Interventions for Adults with a History of Complex Traumatic Events: the Incite Mixed-Methods Systematic Review

Journals Library

Health Technology Assessment Volume 24 • Issue 43 • September 2020 ISSN 1366-5278

Interventions for adults with a history of complex traumatic events: the INCiTE mixed-methods systematic review

Hollie Melton, Nick Meader, Holly Dale, Kath Wright, Julie Jones-Diette, Melanie Temple, Iram Shah, Karina Lovell, Dean McMillan, Rachel Churchill, Corrado Barbui, Simon Gilbody and Peter Coventry

DOI 10.3310/hta24430

Interventions for adults with a history of complex traumatic events: the INCiTE mixed-methods systematic review

Hollie Meltono ,1 Nick Meadero ,1 Holly Daleo ,2 Kath Wrighto ,1 Julie Jones-Dietteo ,1 Melanie Templeo ,3 Iram Shaho ,3 Karina Lovello ,4 Dean McMillano ,5,6 Rachel Churchillo ,1 Corrado Barbuio ,7 Simon Gilbodyo 5,6 and Peter Coventryo 1,5*

1Centre for Reviews and Dissemination, University of York, York, UK 2School of Health Sciences, University of Manchester, Manchester, UK 3Schoen Clinic, York, UK 4Division of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK 5Department of Health Sciences, University of York, York, UK 6Hull York Medical School, University of York, York, UK 7Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy

*Corresponding author

Declared competing interests of authors: Rachel Churchill was part of a Systematic Reviews Programme Advisory Group. Simon Gilbody is/was a member of the following committees: Health Technology Assessment (HTA) Clinical Trials Board (2008–14), HTA Commissioning Board (2016–19), HTA Efficient Study Designs (2015–16), HTA End of Life Care and Add on Studies (2016), HTA Funding Boards Policy Group (formerly CSG) (2017–20), HTA Funding Teleconference Members (2015–16) and HTA Post-board Funding Teleconference (2017–20). Peter Coventry is a member of the following committees: HTA General Board (2018–19) and Health Services and Delivery Research Funding Committee Members (2019–22).

Published September 2020 DOI: 10.3310/hta24430

This report should be referenced as follows:

Melton H, Meader N, Dale H, Wright K, Jones-Diette J, Temple M, et al. Interventions for adults with a history of complex traumatic events: the INCiTE mixed-methods systematic review. Health Technol Assess 2020;24(43).

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© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

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NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Abstract

Interventions for adults with a history of complex traumatic events: the INCiTE mixed-methods systematic review

*Corresponding author [email protected]

Background: People with a history of complex traumatic events typically experience trauma and stressor disorders and additional mental comorbidities. It is not known if existing evidence-based treatments are effective and acceptable for this group of people. Objective: To identify candidate psychological and non-pharmacological treatments for future research. Design: Mixed-methods systematic review. Participants: Adults aged ≥ 18 years with a history of complex traumatic events. Interventions: Psychological interventions versus control or active control; pharmacological interventions versus placebo. Main outcome measures: Post-traumatic stress disorder symptoms, common mental health problems and attrition. Data sources: Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 onwards); Cochrane Central Register of Controlled Trials (CENTRAL) (from inception); EMBASE (1974 to 2017 week 16); International Pharmaceutical Abstracts (1970 onwards); MEDLINE and MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations (1946 to present); Published International Literature on Traumatic Stress (PILOTS) (1987 onwards); PsycINFO (1806 to April week 2 2017); and Science Citation Index (1900 onwards). Searches were conducted between April and August 2017. Review methods: Eligible studies were singly screened and disagreements were resolved at consensus meetings. The risk of bias was assessed using the Cochrane risk-of-bias tool and a bespoke version of a quality appraisal checklist used by the National Institute for Health and Care Excellence. A meta-analysis was conducted across all populations for each intervention category and for population subgroups. Moderators of effectiveness were assessed using metaregression and a component network meta-analysis. A qualitative synthesis was undertaken to summarise the acceptability of interventions with the relevance of findings assessed by the GRADE-CERQual checklist.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in vii professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. ABSTRACT

Results: One hundred and four randomised controlled trials and nine non-randomised controlled trials were included. For the qualitative acceptability review, 4324 records were identified and nine studies were included. The population subgroups were veterans, childhood sexual abuse victims, war affected, refugees and domestic violence victims. Psychological interventions were superior to the control post treatment for reducing post-traumatic stress disorder symptoms (standardised mean difference –0.90, 95% confidence interval –1.14 to –0.66; number of trials = 39) and also for associated symptoms of depression, but not anxiety. Trauma-focused therapies were the most effective interventions across all populations for post-traumatic stress disorder and depression. Multicomponent and trauma-focused interventions were effective for negative self-concept. Phase-based approaches were also superior to the control for post-traumatic stress disorder and depression and showed the most benefit for managing emotional dysregulation and interpersonal problems. Only antipsychotic medication was effective for reducing post-traumatic stress disorder symptoms; medications were not effective for mental comorbidities. Eight qualitative studies were included. Interventions were more acceptable if service users could identify benefits and if they were delivered in ways that accommodated their personal and social needs. Limitations: Assessments about long-term effectiveness of interventions were not possible. Studies that included outcomes related to comorbid psychiatric states, such as borderline personality disorder, and populations from prisons and humanitarian crises were under-represented. Conclusions: Evidence-based psychological interventions are effective and acceptable post treatment for reducing post-traumatic stress disorder symptoms and depression and anxiety in people with complex trauma. These interventions were less effective in veterans and had less of an impact on symptoms associated with complex post-traumatic stress disorder. Future work: Definitive trials of phase-based versus non-phase-based interventions with long-term follow-up for post-traumatic stress disorder and associated mental comorbidities. Study registration: This study is registered as PROSPERO CRD42017055523. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 43. See the NIHR Journals Library website for further project information.

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NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Contents

List of tables xiii

List of figures xvii

List of abbreviations xxv

Plain English summary xxvii

Scientific summary xxix

Chapter 1 Background 1 Trauma- and stressor-related disorders and their relevance to complex traumatic events 1 Impact and burden of complex trauma 2 Treating mental health problems in people affected by complex trauma 2 Rationale and aims of this review 3

Chapter 2 Methods of the effectiveness review and meta-analysis 5 Aims and objectives 5 Literature searches 5 Inclusion and exclusion criteria 6 Population 6 Interventions 6 Comparators 7 Outcomes 8 Study selection 8 Advisory group 9 Data extraction 9 Risk of bias 9 Randomised controlled studies of clinical effectiveness 9 Non-randomised controlled intervention studies 10 Data analysis 10 Meta-analyses of clinical effectiveness and attrition 10 Subgroup analyses: categorising interventions 11 Meta-regression analyses: predictors of treatment effectiveness 11 Components network meta-analyses 12 Acceptability sensitivity analyses 13

Chapter 3 Methods of the qualitative acceptability review 15 Objective 15 Literature searches 15 Study selection 15 Population 15 Interventions 15 Comparators 15 Outcomes 15 Data extraction 16 Quality assessment 16 Data analysis 16

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in ix professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. CONTENTS

Chapter 4 Results of the effectiveness review 17 Flow of the studies included 17 Studies included 17 Characteristics of the randomised controlled trials included 17 Characteristics of the non-randomised controlled trials included 18 Quality of the studies included 19 Randomised controlled trials 19 Non-randomised controlled trials 20 Meta-analyses of clinical effectiveness 20 All populations and trauma exposure combined 23 Psychological interventions versus control 33 Pharmacological interventions versus placebo 43 Meta-analysis of attrition 45 Intervention categories 45 Trauma populations 47 Meta-regression analyses: predictors of treatment effectiveness 48 Model 1: predictors of treatment effectiveness by population type 48 Model 2: predictors of treatment effectiveness by intervention components 48 Model 3: treatment effectiveness by delivery method 48 Components network meta-analyses 49 Model selection 49 Findings from the intervention component network meta-analysis (model 3) 50 Acceptability sensitivity analyses 51 Adverse events for pharmacological interventions 52 Non-randomised studies of clinical effectiveness 54 Post-traumatic stress disorder symptoms 54 Depression 55 Anxiety 56 Quality of life 57 Sleep quality 57 Attrition 57

Chapter 5 Results of the qualitative acceptability review 59 Studies included 59 Quality of the studies included: Critical Appraisal Skills Programme assessment 61 Narrative synthesis 61 Therapeutic context 61 Skills strengthening 62 Self-efficacy and reward 63 Summary 64

Chapter 6 Patient and public involvement and the research prioritisation exercise 65 Aims 65 Aim 1: consultation on the overall aims and design of the review 65 Methods 65 Participants 65 Format and timing of focus groups 66 Topic guide 66 Results 66 Aims 2 and 3: setting research priorities and disseminating findings 67 Process 67 Results 68

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Chapter 7 Discussion 71 Summary of results across all populations with complex trauma for post-traumatic stress disorder 71 Summary of results for psychological interventions across populations for depression and anxiety 72 Summary of population subgroup analyses 72 Summary of results of pharmacological interventions 74 Heterogeneity 74 Component network meta-analysis 75 Attrition 76 Acceptability and feasibility of interventions: qualitative findings 76 Comparison with other reviews and guidance 76 Strengths and limitations 78 Conclusions and implications for research 80

Acknowledgements 83

References 85

Appendix 1 Literature search strategies for the effectiveness review 121

Appendix 2 Literature search strategies for the qualitative acceptability review 159

Appendix 3 List of studies excluded, with reasons 175

Appendix 4 Characteristics of randomised controlled trials included 185

Appendix 5 Population characteristics of included randomised controlled trials 213

Appendix 6 Characteristics of included non-randomised controlled studies 235

Appendix 7 Population characteristics of included non-randomised controlled studies 237

Appendix 8 Risk-of-bias gradings of included randomised controlled trials 241

Appendix 9 Summary tables of clinical effectiveness analyses 243

Appendix 10 Forest plots of results of effectiveness meta-analyses 267

Appendix 11 Characteristics of qualitative studies included 309

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xi professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

List of tables

TABLE 1 Risk-of-bias gradings for the non-randomised controlled studies included 21

TABLE 2 Predictors of effectiveness of psychological interventions by population type (univariable analyses) 48

TABLE 3 Univariable predictors of treatment effectiveness by intervention component 49

TABLE 4 Predictors of treatment effectiveness by delivery method 49

TABLE 5 Comparing the goodness of fit for different component network meta-analysis models 50

TABLE 6 Mean difference for outcomes by intervention component 51

TABLE 7 Odds ratios of attrition per population shown across all studies and across only those trials rated as being at a low risk of attrition bias 52

TABLE 8 Pharmacological intervention withdrawals and adverse events as reported 52

TABLE 9 Non-randomised trial intervention characteristics and effects on PTSD outcomes 54

TABLE 10 Non-randomised trial intervention characteristics and effects on depression outcomes 56

TABLE 11 Non-randomised trial intervention characteristics and effects on anxiety outcomes 56

TABLE 12 Odds ratios of attrition for each trial reporting data 57

TABLE 13 Risk-of-bias assessment of the qualitative studies included using the CASP tool 60

TABLE 14 Research priorities developed from research prioritisation exercise attendees and the share of the online vote 69

TABLE 15 Search strategy for CINAHL via EBSCOhost 121

TABLE 16 Search strategy for CENTRAL via The Cochrane Library 124

TABLE 17 Search strategy for EMBASE via Ovid 133

TABLE 18 Search strategy for International Pharmaceutical Abstracts via ProQuest 138

TABLE 19 Search strategy for MEDLINE via Ovid 138

TABLE 20 Search strategy for PILOTS via ProQuest 143

TABLE 21 Search strategy for PsycINFO via Ovid 150

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xiii professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. LIST OF TABLES

TABLE 22 Search strategy for Science Citation Index via Web of Science 156

TABLE 23 Search strategy for CINAHL via EBSCOhost 159

TABLE 24 Search strategy for EMBASE via Ovid 162

TABLE 25 Search strategy for MEDLINE via Ovid 166

TABLE 26 Search strategy for PsycINFO via Ovid 170

TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion 175

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions 186

TABLE 29 Intervention characteristics for randomised controlled studies included comparing pharmacological interventions 203

TABLE 30 Intervention characteristics for randomised controlled studies included comparing combined psychological and pharmacological interventions 208

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included 214

TABLE 32 Characteristics of the interventions in the non-randomised controlled studies of intervention effectiveness included 235

TABLE 33 Population characteristics of the non-randomised studies of intervention effectiveness included 238

TABLE 34 Effectiveness of psychological interventions on PTSD outcomes for all trauma populations 244

TABLE 35 Effectiveness of psychological interventions on CPTSD outcomes for all trauma populations 245

TABLE 36 Effectiveness of psychological interventions on depression outcomes for all trauma populations 247

TABLE 37 Effectiveness of psychological interventions on anxiety outcomes for all trauma populations 248

TABLE 38 Effectiveness of psychological interventions on quality-of-life outcomes for all trauma populations 249

TABLE 39 Effectiveness of psychological interventions on sleep quality outcomes for all trauma populations 250

TABLE 40 Effectiveness of psychological interventions for veteran populations 251

TABLE 41 Effectiveness of psychological interventions for war-affected populations 254

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TABLE 42 Effectiveness of psychological interventions for childhood sexual abuse populations 256

TABLE 43 Effectiveness of psychological interventions for refugee populations 258

TABLE 44 Effectiveness of psychological interventions for domestic violence populations 261

TABLE 45 Effectiveness of pharmacological interventions on PTSD outcomes for veteran populations 263

TABLE 46 Effectiveness of pharmacological interventions on depression outcomes for veteran populations 263

TABLE 47 Effectiveness of pharmacological interventions on psychosis outcomes for veteran populations 264

TABLE 48 Effectiveness of pharmacological interventions on sleep quality outcomes for veteran populations 265

TABLE 49 Characteristics of the qualitative studies included 310

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xv professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

List of figures

FIGURE 1 The PRISMA flow diagram indicating the flow of studies through the review process 17

FIGURE 2 Proportional distribution of the risk-of-bias grades across the RCTs included per domain of bias 19

FIGURE 3 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all psychological interventions with control 24

FIGURE 4 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing phase-based psychological interventions with control 25

FIGURE 5 Meta-analysis of post-treatment SMD for emotional dysregulation, comparing all psychological interventions with control 26

FIGURE 6 Meta-analysis of post-treatment SMD for emotional dysregulation, comparing phase-based psychological interventions with control 27

FIGURE 7 Meta-analysis of post-treatment SMD for negative self-concept, comparing all psychological interventions with control (positive SMD equals improvement in symptoms) 27

FIGURE 8 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all psychological interventions with control 29

FIGURE 9 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing phase-based interventions with control 30

FIGURE 10 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing all psychological interventions with control 31

FIGURE 11 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing trauma-focused CBT with control 31

FIGURE 12 Meta-analysis of post-treatment effect size (ES) for quality of life, comparing all psychological interventions with control (positive ES favours intervention) 32

FIGURE 13 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing all psychological interventions with control in veteran populations 33

FIGURE 14 Meta-analysis of post-treatment SMD for total depression symptoms, comparing all psychological interventions with control in veteran populations 35

FIGURE 15 Meta-analysis of post-treatment SMD for total anxiety symptoms, comparing all psychological interventions with control in veteran populations 36

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xvii professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. LIST OF FIGURES

FIGURE 16 Meta-analysis of post-treatment effect size (ES) for total PTSD symptoms, comparing all psychological interventions with control in war-affected populations 37

FIGURE 17 Meta-analysis of post-treatment effect size (ES) for total depression symptoms, comparing all trauma-focused CBT interventions with control in war-affected populations 38

FIGURE 18 Meta-analysis of post-treatment effect size (ES) for total anxiety symptoms, comparing trauma-focused CBT with control in war-affected populations 38

FIGURE 19 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing all psychological interventions with control in childhood sexual abuse populations 39

FIGURE 20 Meta-analysis of post-treatment SMD for depression symptoms, comparing all psychological interventions with control in childhood sexual abuse populations 40

FIGURE 21 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing all psychological interventions with control in refugee populations 42

FIGURE 22 Meta-analysis of post-treatment SMD for depression symptoms, comparing all psychological interventions with control in refugee populations 42

FIGURE 23 Meta-analysis of ORs of attrition for trauma-focused CBT interventions compared with control 46

FIGURE 24 Network plot for all combinations of components extracted from the studies included 50

FIGURE 25 The PRISMA diagram of the flow of records through the review process 59

FIGURE 26 Risk-of-bias ratings across the domains of the Cochrane tool for all included RCTs 242

FIGURE 27 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all IPT interventions with control 267

FIGURE 28 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all trauma-focused CBT interventions with control 268

FIGURE 29 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all EMDR interventions with control 269

FIGURE 30 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all mindfulness interventions with control 269

FIGURE 31 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all non-trauma-focused CBT interventions with control 270

FIGURE 32 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all single-component trauma-focused interventions with control 270

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FIGURE 33 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all multicomponent trauma-focused interventions with control 271

FIGURE 34 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all single-component non-trauma-focused interventions with control 271

FIGURE 35 Meta-analysis of post-treatment SMD for emotional dysregulation, comparing trauma-focused CBT interventions with control 272

FIGURE 36 Meta-analysis of post-treatment SMD for emotional dysregulation, comparing single-component and non-trauma-focused interventions with control 272

FIGURE 37 Meta-analysis of post-treatment SMD for negative self-concept, comparing all trauma-focused CBT interventions with control (positive SMD equals improvement in symptoms) 273

FIGURE 38 Meta-analysis of post-treatment SMD for negative self-concept, comparing all multicomponent and trauma-focused interventions with control (positive SMD equals improvement in symptoms) 273

FIGURE 39 Meta-analysis of post-treatment SMD for negative self-concept, comparing all single-component and non-trauma-focused interventions with control (positive SMD equals improvement in symptoms) 273

FIGURE 40 Meta-analysis of post-treatment SMD for interpersonal problems, comparing all psychological interventions with control 274

FIGURE 41 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all trauma-focused CBT interventions with control 274

FIGURE 42 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all EMDR interventions with control 275

FIGURE 43 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all IPT interventions with control 275

FIGURE 44 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all mindfulness interventions with control 276

FIGURE 45 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all non-trauma-focused CBT interventions with control 276

FIGURE 46 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all single-component and trauma-focused CBT interventions with control 277

FIGURE 47 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all multicomponent and trauma-focused interventions with control 277

FIGURE 48 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all single-component and non-trauma-focused interventions with control 278

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xix professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. LIST OF FIGURES

FIGURE 49 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing EMDR interventions with control 278

FIGURE 50 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing single-component and trauma-focused interventions with control 279

FIGURE 51 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing multicomponent and trauma-focused interventions with control 279

FIGURE 52 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing single-component and non-trauma-focused interventions with control 280

FIGURE 53 Meta-analysis of post-treatment effect size (ES) for quality of life, comparing trauma-focused CBT interventions with control (positive ES favours intervention) 280

FIGURE 54 Meta-analysis of post-treatment effect size (ES) for sleep quality, comparing all psychological interventions with control 281

FIGURE 55 Meta-analysis of post-treatment effect size (ES) for sleep quality, comparing trauma-focused CBT interventions with control 281

FIGURE 56 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing trauma-focused CBT interventions with control in veteran populations 282

FIGURE 57 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing EMDR interventions with control in veteran populations 282

FIGURE 58 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing mindfulness interventions with control in veteran populations 283

FIGURE 59 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and trauma-focused interventions with control in veteran populations 283

FIGURE 60 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing multicomponent and trauma-focused interventions with control in veteran populations 284

FIGURE 61 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and non-trauma-focused interventions with control in veteran populations 284

FIGURE 62 Meta-analysis of post-treatment SMD for total depression symptoms, comparing trauma-focused CBT interventions with control in veteran populations 285

FIGURE 63 Meta-analysis of post-treatment SMD for total depression symptoms, comparing EMDR interventions with control in veteran populations 285

FIGURE 64 Meta-analysis of post-treatment SMD for total depression symptoms, comparing mindfulness interventions with control in veteran populations 286

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

FIGURE 65 Meta-analysis of post-treatment SMD for total depression symptoms, comparing single-component and trauma-focused interventions with control in veteran populations 286

FIGURE 66 Meta-analysis of post-treatment SMD for total depression symptoms, comparing multicomponent and trauma-focused interventions with control in veteran populations 287

FIGURE 67 Meta-analysis of post-treatment SMD for total depression symptoms, comparing single-component and non-trauma-focused interventions with control in veteran populations 287

FIGURE 68 Meta-analysis of post-treatment SMD for total anxiety symptoms, comparing trauma-focused CBT interventions with control in veteran populations 288

FIGURE 69 Meta-analysis of post-treatment SMD for total anxiety symptoms, comparing EMDR interventions with control in veteran populations 288

FIGURE 70 Meta-analysis of post-treatment effect size (ES) for total PTSD symptoms, comparing trauma-focused CBT interventions with control in war-affected populations 289

FIGURE 71 Meta-analysis of post-treatment effect size (ES) for total PTSD symptoms, comparing multicomponent trauma-focused interventions with control in war-affected populations 289

FIGURE 72 Meta-analysis of post-treatment SMD for depression symptoms, comparing single-component and trauma-focused interventions with control in war-affected populations 290

FIGURE 73 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing multicomponent and trauma-focused interventions with control in war-affected populations 290

FIGURE 74 Meta-analysis of post-treatment SMD for total anxiety symptoms, comparing single-component and trauma-focused interventions with control in war-affected populations 291

FIGURE 75 Meta-analysis of post-treatment effect size (ES) for total anxiety symptoms, comparing multicomponent and trauma-focused interventions with control in war-affected populations 291

FIGURE 76 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing trauma-focused CBT interventions with control in childhood sexual abuse populations 292

FIGURE 77 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing non-trauma-focused CBT interventions with control in childhood sexual abuse populations 292

FIGURE 78 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and trauma-focused interventions with control in childhood sexual abuse populations 293

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xxi professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. LIST OF FIGURES

FIGURE 79 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and non-trauma-focused interventions with control in childhood sexual abuse populations 293

FIGURE 80 Meta-analysis of post-treatment SMD for depression symptoms, comparing trauma-focused CBT interventions with control in childhood sexual abuse populations 294

FIGURE 81 Meta-analysis of post-treatment SMD for depression symptoms, comparing single-component and trauma-focused interventions with control in childhood sexual abuse populations 294

FIGURE 82 Meta-analysis of post-treatment SMD for depression symptoms, comparing single-component and non-trauma-focused interventions with control in childhood sexual abuse populations 295

FIGURE 83 Meta-analysis of post-treatment SMD for anxiety symptoms, comparing single-component and trauma-focused interventions with control in childhood sexual abuse populations 295

FIGURE 84 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing trauma-focused CBT interventions with control in refugee populations 296

FIGURE 85 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing EMDR interventions with control in refugee populations 296

FIGURE 86 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and trauma-focused interventions with control in refugee populations 297

FIGURE 87 Meta-analysis of post-treatment SMD for depression symptoms, comparing trauma-focused CBT interventions with control in refugee populations 297

FIGURE 88 Meta-analysis of post-treatment SMD for depression symptoms, comparing EMDR interventions with control in refugee populations 298

FIGURE 89 Meta-analysis of post-treatment SMD for depression symptoms, comparing single-component and trauma-focused interventions with control in refugee populations 298

FIGURE 90 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing antidepressants with placebo 299

FIGURE 91 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing SSRIs with placebo 299

FIGURE 92 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing antipsychotics with placebo 300

FIGURE 93 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing anticonvulsants with placebo 300

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FIGURE 94 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing prazosin with placebo 300

FIGURE 95 Meta-analysis of post-treatment SMD for depression symptoms, comparing antidepressants with placebo 301

FIGURE 96 Meta-analysis of post-treatment SMD for depression symptoms, comparing antipsychotics with placebo 301

FIGURE 97 Meta-analysis of post-treatment SMD for depression symptoms, comparing anticonvulsants with placebo 301

FIGURE 98 Meta-analysis of post-treatment weighted mean difference (WMD) for positive psychotic symptoms, comparing risperidone with placebo 302

FIGURE 99 Meta-analysis of post-treatment weighted mean difference (WMD) for negative psychotic symptoms, comparing risperidone with placebo 302

FIGURE 100 Meta-analysis of post-treatment weighted mean difference (WMD) for total psychotic symptoms, comparing risperidone with placebo 302

FIGURE 101 Meta-analysis of post-treatment weighted mean difference (WMD) for general psychopathology symptoms, comparing risperidone with placebo 303

FIGURE 102 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a veteran population 303

FIGURE 103 Meta-analysis of OR of attrition from all psychological interventions compared with active controls, among a veteran population 304

FIGURE 104 Meta-analysis of OR of attrition from antidepressants compared with placebo, among a veteran population 304

FIGURE 105 Meta-analysis of OR of attrition from antidepsychotics compared with placebo, among a veteran population 305

FIGURE 106 Meta-analysis of OR of attrition from anticonvulsants compared with placebo, among a veteran population 305

FIGURE 107 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a childhood sexual abuse population 306

FIGURE 108 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a refugee population 306

FIGURE 109 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a domestic violence population 307

FIGURE 110 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a war-affected population 307

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xxiii professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

List of abbreviations

CAPS Clinician-Administered ISTSS International Society for PTSD Scale Traumatic Stress Studies CASP Critical Appraisal Skills MBSR mindfulness-based stress Programme reduction CBT cognitive–behavioural therapy NA not applicable CENTRAL Cochrane Central Register of NET narrative exposure therapy Controlled Trials NICE National Institute for Health and CI confidence interval Care Excellence CINAHL Cumulative Index to Nursing and NR did not report information Allied Health Literature OR odds ratio CPT cognitive processing therapy PANSS Positive and Negative CPTSD complex post-traumatic stress Syndrome Scale disorder PILOTS Published International Literature DBT dialectical behaviour therapy On Traumatic Stress DESNOS disorders of extreme stress not PPI patient and public involvement otherwise specified PTSD post-traumatic stress disorder DIC deviance information criterion RCT randomised controlled trial DSM Diagnostic and Statistical Manual of ROBINS-I Risk Of Bias In Non-randomized Mental Disorders Studies – of Interventions EMDR eye movement desensitisation SE standard error and reprocessing SMD standardised mean difference ICD International Classification of Diseases SSRI selective serotonin reuptake inhibitor ICD-10 International Classification of Diseases, Tenth Revision STAIR Skills Training in Affect and Interpersonal Regulation INCiTE INterventions for Complex Traumatic Events WHO World Health Organization IPT interpersonal psychotherapy

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xxv professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Plain English summary

raumatic events that happen often and that are difficult to escape from, such as childhood abuse, Tare sometimes known as complex traumatic events. People who have a history of complex traumatic events can develop post-traumatic stress disorder and can also suffer from other mental health problems. It is not known if people who experience complex traumatic events can benefit from existing psychological treatments or medications, or if these treatments are acceptable. This review aimed to find out which treatments are most effective and acceptable for mental health problems in people with complex trauma histories, and to identify the frontrunners for future research. We searched electronic databases for evidence about treatment effectiveness and acceptability in adults with a history of complex traumatic events. We found 104 randomised controlled trials and nine non-randomised controlled trials that tested the effectiveness of psychological and/or medications, as well as nine studies that used interviews and focus groups to describe the acceptability of psychological treatments. The studies were split across different populations that included veterans, refugees, people who had experienced childhood sexual abuse and domestic violence, and civilians affected by war. We found that psychological treatments that focused on improving symptoms associated with trauma were effective for reducing post-traumatic stress disorder symptoms and depression across all populations and fewer people dropped out of these treatments, suggesting that they are acceptable. However, trauma-focused treatments were less effective among veterans than among other groups and less effective for reducing other psychological symptoms commonly experienced by people with complex trauma histories. Phased treatments that first start with helping people to feel safe before focusing on trauma symptoms might be beneficial for both post-traumatic stress disorder and additional psychological symptoms. There was little evidence that medications, other than antipsychotics, were effective for post-traumatic stress disorder symptoms. Future work should test if phased treatments are more effective than non-phased treatments over the long term.

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DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Scientific summary

Background

There is growing evidence that, in addition to post-traumatic stress disorder symptoms, exposure to prolonged and repetitive trauma of an interpersonal nature, such as childhood sexual abuse, is associated with mental health symptoms related to problems of emotional regulation, negative self-concept and interpersonal dysfunction. To better capture the symptom profile of people exposed to prolonged and multiple forms of trauma, a separate diagnosis of complex post-traumatic stress disorder has been proposed as part of the new International Classification of Diseases, Eleventh Edition.

Evidence-based treatments exist for single-event post-traumatic stress disorder and these include trauma-focused psychological interventions, which are recommended as first-line therapies, and also pharmacological therapies. However, it is not known if these therapeutic approaches are effective for people with a history of complex trauma or if they are safe and acceptable among this population. People with complex mixes of comorbidities may be excluded from clinical trials and they are further disadvantaged because their health needs are not well met by health services, such as Improving Access to Psychological Therapy services.

Complex trauma is increasingly prominent and relevant to the NHS, but existing mental health services are not well equipped to appropriately manage patients with complex traumatic histories. There is a need to identify candidate psychological and pharmacological treatments for this group with a view to informing practice and prioritising future research.

Objectives

The primary research question set by the Health Technology Assessment programme was the following: how effective are interventions that treat mental health problems associated with a history of complex traumatic events? The funding brief further elaborated on this research question by stating that the global objective was to undertake a broad evidence synthesis that builds on and extends previous reviews, reflective of the patient group seen in clinical practice, and to include pharmacological as well as non-pharmacological interventions. A key objective was to identify leading candidate interventions that the Health Technology Assessment programme could fund as part of a future round of primary research.

To achieve these objectives, we specifically aimed to: l descriptively synthesise evidence from randomised and non-randomised controlled trials of psychological and/or pharmacological interventions for mental health in people with a history of complex traumatic events l quantitatively assess, with meta-analysis if feasible, the clinical effectiveness of interventions delivered to adults, aged ≥ 18 years, with trauma and stressor disorders after exposure to complex traumatic events l provide evaluations of the comparative clinical effectiveness of psychological interventions and pharmacological interventions using a network meta-analysis

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xxix professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. SCIENTIFIC SUMMARY

l identify, appraise and synthesise qualitative and quantitative data that address service user and provider perspectives about the acceptability and feasibility of using psychological and/or pharmacological interventions to treat mental health problems after complex traumatic events l identify leading candidate interventions that could be feasibly tested and used in the NHS and make recommendations to the Health Technology Assessment programme about future research priorities.

Methods

A mixed-methods systematic review was conducted that included eligible studies to address questions about the effectiveness and acceptability of psychological and/or pharmacological interventions for mental health problems in adults, aged ≥ 18 years, with a history of complex trauma. The methods for screening and data extraction and analysis followed guidance from the Cochrane Collaboration and the Centre for Reviews and Dissemination.

The quantitative and qualitative findings were presented at a stakeholder research prioritisation day attended by the research team, as well as by practitioners with an interest and experience in complex trauma, by voluntary and third-sector providers of services to people affected by complex trauma, and by experts through experience. Research priorities were co-produced during workshops and ranked following an online voting exercise, which was facilitated by the Beyond The Room (http://beyondtheroom.net/).

Data sources

l Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCOhost (1937 onwards; search date: 20 April 2017). l Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane Library (from inception; search date: 21 April 2017). l EMBASE via Ovid (1974 to 2017 week 16; search date: 19 April 2017). l International Pharmaceutical Abstracts via ProQuest (1970 onwards; search date: 30 August 2017). l MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE via Ovid (1946 to present; search date: 18 April 2017). l Published International Literature On Traumatic Stress (PILOTS) via ProQuest (1987 onwards; search date: 2 May 2017). l PsycINFO via Ovid (1806 to April week 2 2017; search date: 18 April 2017). l Science Citation Index via Web of Science (1900 onwards; search date: 20 April 2017).

Two separate searches were run to capture eligible studies relevant to questions of effectiveness and acceptability of interventions.

Study selection

We identified the population of interest as adults, aged ≥ 18 years, exposed to deliberate and premeditated events, to a series of events that were extreme and prolonged or to events of a repetitive nature from which escape was difficult or impossible. Studies were included if they assessed treatment effectiveness and acceptability in this population. This approach approximated the definition of complex trauma used to describe complex post-traumatic stress disorder, although we did not use the newly defined International Classification of Diseases, Eleventh Edition, diagnostic category of complex post-traumatic stress disorder to search for eligible studies. Eligible studies for the effectiveness review needed to be randomised or non-randomised controlled trials and needed to measure post-traumatic stress disorder and/or mental health outcomes. Eligible studies for the qualitative acceptability review

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needed to have used qualitative methods, such as in-depth interviews or focus groups. Studies that evaluated any first- or second-line psychological therapy that aimed to improve symptoms (including comorbidities) of trauma- and stressor-related disorders, delivered to either individuals or groups, were included. Complementary and alternative therapeutic interventions were excluded. All drug treatments subjected to experimental testing in the context of the treatment of mental health problems in people with a history of complex trauma were considered for inclusion.

Data extraction

Data were singly extracted by the review team using a prespecified data extraction Microsoft Excel® (Microsoft Corporation, Redmond, WA, USA) spreadsheet that included domains for study and participant characteristics, outcomes and attrition. The risk of bias for randomised controlled trials was assessed using the Cochrane risk-of-bias tool. The risk of bias for non-randomised controlled intervention studies was assessed using a bespoke version of a quality appraisal checklist used by the National Institute for Health and Care Excellence in public health guidance, and based on the Graphical Appraisal Tool for Epidemiological studies.

Quality assessments of the qualitative data were undertaken using the Critical Appraisal Skills Programme checklist and the validity and relevance of the data to the questions were assessed using the GRADE-CERQual checklist.

Data synthesis

For the quantitative review of effectiveness, we undertook a series of meta-analyses that pooled results across all populations for each intervention category. Mean differences and 95% confidence intervals were computed for outcomes measured using the same scale. Standardised mean differences with 95% confidence intervals were computed for outcomes measured using different scales. We also evaluated the effectiveness of interventions with a meta-analysis across population subgroups. In addition to the meta-analyses, we explored if the treatment effects of interventions were moderated by population subgroup, intervention components and delivery methods (e.g. individual or group). We further explored whether or not certain components of composite interventions were more effective than each other using a component network meta-analysis.

For the qualitative review of acceptability of interventions, we undertook a narrative synthesis of qualitative data extracted from the included studies, mapping data to themes and subthemes related to acceptability and feasibility.

Results

In the effectiveness review, 104 studies were included. Of these, 95 were randomised controlled trials and nine were non-randomised controlled trials. The population subgroups that were included were veterans, childhood sexual abuse, war affected, refugees and domestic violence.

Effectiveness of psychological interventions across all populations

The pooled results across all populations with complex trauma showed that existing evidence-based psychological interventions were effective at reducing post-traumatic stress disorder symptoms when compared with the control post treatment (standardised mean difference –0.90, 95% confidence

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interval –1.14 to –0.66; number of trials = 39), and there was some evidence that this finding held when treatment effects were measured up to 6 months post treatment. Trauma-focused cognitive–behavioural therapy and more broadly single-component and trauma-focused interventions were more effective than the control post treatment and at follow-up. Multicomponent and trauma-focused interventions for post-traumatic stress disorder symptoms post treatment were also effective, but the treatment effects were smaller than for single-component and trauma-focused interventions.

For the symptom cluster associated with complex post-traumatic stress disorder, we found no evidence that either trauma- or non-trauma-focused psychological interventions were superior in improving emotional dysregulation or interpersonal problems. Multicomponent and single-component trauma- focused interventions showed benefits for negative self-concept. Phase-based interventions that included stabilisation work before exposure therapy had positive effects on emotional dysregulation and interpersonal problems, although the results for these outcomes were of borderline significance.

Collectively, psychological interventions were superior to the control, but not the active control, post treatment and at follow-up for managing associated symptoms of depression in all populations with complex trauma (standardised mean difference –0.94, 95% confidence interval –1.20 to –0.68; number of trials = 22). The most consistent and the largest effects for depression across all time points were observed in trials that tested single-component and trauma-focused interventions. Similarly, pooled results showed that psychological interventions of any type were effective for reducing anxiety in all populations with complex trauma (standardised mean difference –0.81, 95% confidence interval –1.18 to –0.46; number of trials = 13). Trauma-focused approaches, when delivered as either a single-component or a multicomponent intervention, were superior to the control for anxiety symptoms when effects were pooled across all populations.

There were insufficient data to assess the effectiveness of psychological interventions for other secondary outcomes.

Effectiveness of psychological interventions across population subgroups

Among veterans, psychological interventions were effective for reducing post-traumatic stress disorder symptoms, but the size of the treatment effect was much smaller than in analyses that pooled results across all populations (standardised mean difference –0.48, 95% confidence interval –0.72 to 0.24; number of trials = 14). Trauma-focused cognitive–behavioural therapy and eye movement desensitisation and reprocessing therapy were the most efficacious treatments in this subgroup for post-traumatic stress disorder, but superior effects were observed when multicomponent and trauma-focused interventions were compared with the control. These two therapies were also effective for reducing depression and anxiety in veterans.

For people exposed to childhood sexual abuse, psychological interventions were effective for reducing post-traumatic stress disorder symptoms (standardised mean difference –0.90, 95% confidence interval –1.43 to –0.37; number of trials = 9). The largest effects for reducing depression in this subgroup were observed in the meta-analysis that compared multicomponent trauma-focused interventions with the control. There was no clear indication about which treatments were effective for reducing anxiety in people with a history of childhood sexual abuse.

Among war-affected populations, psychological interventions as a whole were effective at reducing symptoms of post-traumatic stress disorder (standardised mean difference –0.46, 95% confidence interval –0.68 to –0.25; number of trials = 8). Individual trauma-focused cognitive–behavioural therapy was the most effective intervention in this subgroup for post-traumatic stress disorder symptoms and for depression; there was insufficient evidence to draw firm conclusions about the effectiveness of interventions for anxiety symptoms among war-affected populations.

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Large and positive effects in favour of psychological interventions for post-traumatic stress disorder symptoms were observed in refugee populations (standardised mean difference –1.84, 95% confidence interval –2.18 to –1.49; number of trials = 6). Trauma-focused cognitive–behavioural therapy and eye movement desensitisation and reprocessing therapy were the most effective interventions for both post-traumatic stress disorder and depression in this subgroup; meta-analyses that assessed the effectiveness of interventions for anxiety among refugees were not possible.

Only two trials were included in the meta-analyses of psychological interventions for people exposed to domestic violence. Trauma-focused cognitive–behavioural therapy was effective for reducing post-traumatic stress disorder and depression in this subgroup.

The meta-regression showed that psychological interventions were most effective for post-traumatic stress disorder symptoms in populations exposed to domestic violence and were least effective among veterans. The component network meta-analysis showed that cognitive restructuring, imaginal exposure and relaxation were effective components of trauma-focused cognitive–behavioural therapy. Mindfulness and phase-based interventions were also effective components of composite interventions for post-traumatic stress disorder symptoms.

Effectiveness of pharmacological interventions

All but one of the six trials that compared pharmacological interventions with placebo were conducted in veterans. Overall, only antipsychotic medicine was effective in reducing post-traumatic stress disorder symptoms in veterans (standardised mean difference –0.45, 95% confidence interval –0.85 to –0.05; number of trials = 5). No pharmacological intervention was effective for reducing symptoms of depression or psychosis in veterans. There was evidence from just two studies that prazosin had positive benefits for sleep quality among veterans.

Quality of evidence

The risk of bias across randomised controlled trials was difficult to ascertain for five of six domains of the Cochrane risk-of-bias tool, owing to inadequate reporting. Only a small proportion (20–30%) of randomised controlled trials were rated as being at low risk of bias for sequence generation, allocation concealment and blinding of outcome assessments, which were the primary indicators of study quality. Similarly, study quality was variable among the non-randomised controlled trials. There was a high risk of bias for outcome assessment, with only three of nine studies taking steps to blind investigators; domains related to allocation bias were poorly reported, leading to judgements that the internal validity of non-randomised trials was low or difficult to assess.

Acceptability of interventions

Eight qualitative studies were included in the acceptability synthesis. The acceptability of interventions was associated with how congruent they were with participants’ therapeutic needs and social contexts, as well as the means by which they were able to provide participants with opportunities to engage in personal and interpersonal improvement and confer demonstrable improvements. The feasibility of interventions hinged on more instrumental features, such as scheduling and timing of treatment sessions.

Conclusions

Trauma-focused cognitive–behavioural therapy and other trauma-focused interventions, including eye movement desensitisation and reprocessing therapy, delivered as single-component or multicomponent approaches, are superior to the control for post-traumatic stress disorder symptoms and associated

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in xxxiii professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. SCIENTIFIC SUMMARY

mental disorder comorbidities. Positive effects were mainly found post treatment, with few studies showing benefit over the long term. The quality of the randomised controlled trial evidence was generally low or sufficiently unclear to be able to make fundamental recommendations about the effectiveness of interventions. We identified only a small subset of evidence from non-randomised controlled studies in which study quality was variable and internal validity was low. The sizes of the positive treatment effects were not evenly distributed across populations exposed to complex trauma, with the smallest effects observed among veterans and war-affected populations and the largest effects observed in those affected by domestic violence. Phase-based interventions, along with non-trauma-focused intervention components including mindfulness and relaxation, are potentially among the most effective approaches for posttraumatic stress disorder symptoms in people with a history of complex trauma, such as childhood sexual abuse. In addition, there is inconclusive evidence that existing trauma-focused interventions are effective in treating the symptom cluster associated with disturbances of self-organisation typically seen in complex post-traumatic stress disorder. There was little evidence of effectiveness of pharmacological interventions for post-traumatic stress disorder or for associated mental comorbidities.

Recommendations for research

Following the research prioritisation day and based on the synthesis of the effectiveness and acceptability reviews, we have identified the following priorities for future research:

l definitive and fully powered evaluations of effectiveness of interventions in complex trauma with long-term follow-up (i.e. at least 12 months), especially in veterans, people exposed to childhood sexual abuse and populations affected by humanitarian crises l qualitative and quantitative process evaluations to assess the relationship between intervention and programme theory and anticipated outputs and trial results l qualitative evaluations of the acceptability and feasibility of interventions among people exposed to complex interventions to inform barriers to and facilitators of treatment uptake, especially in refugees and asylum seekers l evaluations of the lived experience of people with a history of complex trauma across population subgroups l safety and adverse event profiles of trauma- and non-trauma-focused interventions for people with complex trauma l a core outcome set for trials in complex trauma that includes outcomes related to disturbances of self-organisation and mental comorbidities l the validity of the new International Classification of Diseases, Eleventh Edition, diagnostic category for complex post-traumatic stress disorder to identify and recruit eligible participants to experimental studies.

Study registration

This study is registered as PROSPERO CRD42017055523.

Funding

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 43. See the NIHR Journals Library website for further project information.

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Chapter 1 Background

Trauma- and stressor-related disorders and their relevance to complex traumatic events

Trauma- and stressor-related disorders, also known as reactions to severe stress and adjustment disorders, are mental health problems directly related to exposure to a traumatic event or series of traumatic events. Post-traumatic stress disorder (PTSD) is among the most common mental health disorders to occur after experiencing (or witnessing) a major traumatic event. Typical symptoms include involuntary re-experiencing of the traumatic event in a vivid and distressing way (e.g. flashbacks, nightmares), avoidance of activities reminiscent of the trauma, persistent numbness, emotional blunting and detachment from other people and previously significant activities, along with hyperarousal in the presence of reminders of the trauma (including hypervigilance, difficulty sleeping, irritability, poor concentration and an exaggerated startle response). People with PTSD may also experience comorbid psychological problems including substance use disorders, depression (with increased risk of suicide) and other anxiety disorders (e.g. panic disorders), and functional somatic syndromes, which can further impair social, educational and occupational functioning.

Post-traumatic stress disorder can occur at any age and it is relatively common, with a lifetime prevalence of 7.8%;1 12-month prevalence ranges from 3% to 4%.2 Rates vary depending on the type of stressor experienced; for example, physical assaults in women are associated with a lifetime prevalence of 29%, combat experience in men is associated with a lifetime prevalence of 39% and lifetime prevalence is 15.4% in people exposed to war and displacement.3

It is argued, however, that the PTSD symptom clusters described in the current and previous versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases, Tenth Revision (ICD-10), do not adequately capture the full range of clinical symptoms exhibited by those who experience complex trauma (i.e. developmentally adverse interpersonal trauma such as prolonged domestic or community violence, childhood abuse, torture or exploitation).4 People who experience complex trauma especially, but not exclusively or necessarily in formative periods, are more at risk of other psychiatric disorders. Complex PTSD (CPTSD) and disorders of extreme stress not otherwise specified (DESNOS) are labels that have been used to define syndromes that involve, in addition to core PTSD symptoms, pathological disassociation, emotional dysregulation, somatisation and altered core schemas about the self, relationships and sustaining beliefs.5

Recent empirical work using latent class analysis in people exposed to different types of acute and chronic stress has gone some way to endorse the distinction (to be included in ICD-11)6 between PTSD and CPTSD, with the CPTSD class scoring highest for symptoms related to affective dysregulation, negative self-concept and interpersonal problems.7,8 The symptom profile of CPTSD is thus characterised by the loss of emotional, social, cognitive and psychological skills, because either the person’sdevelopment has been interrupted during a formative phase or they have been seriously impaired owing to exposure to complex trauma. Beyond the prototypical case of childhood sexual abuse, complex trauma experiences have also come to embrace ‘other types of catastrophic, deleterious and entrapping traumatisation occurring in childhood and/or adulthood, such as repeated domestic violence, trafficking and exploitation, and being forcibly displaced’.9 Compared with single-event PTSD, complex trauma is characterised by sustained or repeated instances of trauma of an interpersonal nature that are ‘extremely threatening or horrific and from which escape is difficult or impossible due to physical, psychological, maturational, family/environmental, or social constraints’.10

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 1 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. BACKGROUND

Impact and burden of complex trauma

Mass conflict, persecution, generalised violence and human rights violations pose a critical threat to global mental health. By the end of 2014, 59.5 million people across the world were forcibly displaced (19.5 million refugees, 1.8 million asylum seekers and 38.2 million internally displaced persons) and this figure has certainly been surpassed owing to exceptional numbers fleeing conflict in the Middle East.11 Asylum trends show that there has been a huge increase in applications in industrialised countries, with 80% being lodged in European countries (82% of these in EU countries); the UK saw a 5% increase in asylum applications from 2013 to 2014.12

Among forcibly displaced people, 30.6% are affected by PTSD; reported torture is consistently the strongest population risk factor associated with PTSD in this group.3 Depression and anxiety occur as frequently as, if not more often than, PTSD among refugees and asylum seekers, with rates as high as 40% observed among some displaced groups.13 Similarly, human trafficking (i.e. recruitment and movement of individuals by force, coercion or deception for exploitative purposes) is associated with high levels of physical and mental health problems.14 Worldwide, up to 2.5 million people are known to be in conditions of forced labour and are exposed to high levels of physical and sexual violence, economic restrictions and controlling behaviour.15 The risk of depression, anxiety and PTSD is significantly higher in women who have been exploited for ≥ 6 months compared with the general population,16 and higher in women trafficked for sexual exploitation than in women trafficked for labour exploitation.17

Other critical cases of complex trauma are associated with exposure to childhood sexual and physical abuse. Although under-reported (one in three cases are not reported), 1 in 20 children has been sexually abused in the UK.18 Victims of child abuse are three times more likely to experience PTSD over their lifetime. Rates of PTSD and alcohol dependence are especially high in women who have experienced childhood abuse and related interpersonal violence. In total, the cost of physical and mental health (depression and PTSD) and substance abuse to the UK is estimated to be £3.2B per year, in part owing to under- and unemployment and the high spend in the criminal justice system, as well as costs attributed to the use of mental health services.19 Stigma, discrimination and depression similarly affect victims of childhood abuse and severely impair their quality of life.

Treating mental health problems in people affected by complex trauma

Existing international guidance makes no distinction between more complex variants of PTSD and recommends the use of trauma-focused therapies for people with comorbidities and PTSD. However, many of the trials included in existing systematic reviews [on which National Institute for Health and Care Excellence (NICE) guidance is based]20 were carried out in North American or Western European countries where the type and severity of trauma experienced by participants may not be comparable to settings and scenarios with a higher risk of prolonged exposure to complex interpersonal trauma. In addition, the World Health Organization (WHO) guideline excluded systematic reviews based on trials of treatment of PTSD in refugee populations.21 As such, it is unclear if treatments that are effective for people with single-event PTSD are equally effective for people exposed to complex traumatic events, who have significantly greater psychological comorbidity and functional impairment than the former group. Standard cognitive and behavioural therapies and exposure-based treatments for PTSD might have limited utility and might be harmful if used prematurely for people with psychological problems following complex traumatic events.22 Many people with CPTSD have high levels of disassociation and psychological comorbidities that might limit their capacity to engage in exposure-based therapies, and findings from effectiveness studies in single-event PTSD cannot be generalised to people with complex trauma.23 Compared with brief trauma-focused treatments, phase-based approaches or sequential interventions that first focus on stabilisation (ensuring individuals’ safety, resolving symptoms – including dissociative symptoms – and increasing emotional, social and psychological competencies),

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followed by processing unresolved aspects of individuals’ trauma, with an emphasis on consolidation of treatment gains to facilitate re-engagement with social, educational or occupational relationships, can be effective in more complex presentations of PTSD following childhood sexual abuse.24

However, the quality of the evidence for the CPTSD expert consensus guidelines is mixed: two studies were not randomised controlled trials (RCTs); only three included an active control and none included head-to-head comparisons with trauma-focused therapies; three studies did not follow up with participants; and all of the evidence was drawn from populations exposed to childhood sexual abuse and no other types of complex trauma, which limits the validity and generalisability of the conclusions.25 Indeed, patients with a history of complex traumatic events might benefit from existing evidence-based psychological and pharmacological treatments. Crumlish and O’Rourke identified 10 trials (n = 528) in a review of psychotherapy for refugees and asylum seekers.26 Cognitive–behavioural therapy (CBT) and narrative exposure therapy (NET) emerged as candidate interventions for reducing core PTSD symptoms, but small sample sizes, inadequate allocation concealment and the use of different comparisons limit the conclusions. Similarly, Palic and Elklit, in a review of 25 experimental and non-experimental studies (n = 1113) of psychosocial treatments for PTSD among refugees, identified CBT as the most effective therapy for reducing PTSD symptoms.27 Trauma-focused therapies such as CBT and NET appear to be equally efficacious across different types of trauma too, including repeated traumatisation. Powers et al., in a review of 13 trials (n = 675), showed that there was no significant difference in effect sizes for prolonged exposure therapy across types of trauma (combat/terror, childhood sexual abuse, rape, mixed; p = 0.14).28

More complex presentations of PTSD include psychiatric comorbidities and there is growing evidence that existing non-phase-based approaches are effective in this group. A wide-ranging review with a meta-analysis that included 148 anxiety-disordered treatment samples (47 in PTSD; combined n = 3534) showed that effect sizes post treatment or at follow-up were generally unrelated to psychiatric comorbidity (for comparisons with active and non-active psychological or pharmacotherapy treatments).29 However, in cases of PTSD, there was a positive association between the presence of comorbidities and the treatment outcome: people with comorbidities did better. More specifically, there is emerging evidence that PTSD symptoms in patients with comorbid dissociation, depression, substance abuse and/or mild borderline personality disorder can be successfully and safely treated with existing evidence-based trauma-focused therapies, and their outcomes are comparable with those for patients without these comorbidities.30 CBT is also possibly the most effective approach for PTSD symptoms when compared with multicomponent interventions that seek to first address additional social and psychological problems in refugees.31

In addition, consistent with NICE guidance, trauma-focused therapies that target PTSD symptoms can have a positive impact on comorbidities. A review of 93 studies with 116 comparisons showed that there was a strong correlation between effect sizes for PTSD and depression outcomes, suggesting that psychological and pharmacological therapies are equally efficacious for PTSD and depressive symptoms.32

Rationale and aims of this review

In summary, there is expert consensus that phase-based approaches effectively treat symptoms associated with CPTSD in adults, but the evidence on which this consensus is based is methodologically weak and exclusively based on studies that recruited participants with childhood abuse; findings might not translate to other populations with complex trauma histories. These consensus guidelines also did not review evidence about the effectiveness of pharmacological interventions in CPTSD. There is accumulating evidence that trauma-focused psychological therapies can reduce PTSD symptoms in people exposed to complex traumatic events who have psychiatric comorbidities. These treatments can also reduce comorbid illness in people with PTSD and can be used safely without a stabilisation phase.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 3 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. BACKGROUND

However, existing reviews of the use of trauma-focused therapies in people with complex trauma histories have focused on narrowly defined population subgroups and we still do not know how effective psychological therapies are across all populations with complex trauma. The comparative effectiveness of psychological interventions for mental health outcomes is also unknown for people with complex trauma histories in all settings. The acceptability of psychological interventions, either phased based or trauma focused, has been less well studied. There are also no comprehensive overviews of the effectiveness of pharmacological interventions in people who have been exposed to complex traumatic events. As such, a broad synthesis of evidence is needed to build on and extend the findings from previous reviews, but uncertainties and questions remain about which interventions warrant further evaluation. Furthermore, both pharmacological and psychological interventions should be included across a wide range of populations with a history of complex traumatic events.

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Chapter 2 Methods of the effectiveness review and meta-analysis

arts of this chapter are based on Coventry et al.33 © 2020 Coventry et al. This is an open access Particle distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Aims and objectives

The aim of this review was to provide a broad synthesis of evidence about the effectiveness of psychological and/or pharmacological interventions to treat mental health problems (with or without PTSD symptoms) in people exposed to complex traumatic events. In addition, where feasible, the review aimed to identify and synthesise qualitative and quantitative evidence about the acceptability and uptake of delivering mental health interventions for people with a history of complex traumatic events. Together, these syntheses aimed to offer estimates of the clinical effectiveness and acceptability of existing and novel treatments and to describe uncertainties about the strength of this evidence to inform a broader understanding about which interventions are likely to be candidates for testing in future definitive trials.

More specifically, the objectives of this review were as follows. l Descriptive synthesis: to provide an overview of existing RCTs and non-RCTs of psychological and/or pharmacological interventions for mental health problems in people with a history of complex traumatic events with specific reference to participant characteristics, intervention format and content, and the outcomes measured. l Clinical effectiveness: narratively and quantitatively, with a meta-analysis if feasible, to report on the clinical effectiveness of interventions delivered to adults aged 18 years and over with trauma and stressor disorders after exposure to complex traumatic events. l Comparative effectiveness: to provide evaluations of comparative clinical effectiveness of psychological interventions (e.g. phase-based vs. conventional trauma-focused therapies) and different pharmacological interventions using a network meta-analysis. l Acceptability and feasibility: to identify, appraise and synthesise narratively qualitative and quantitative data that address service user and provider perspectives about the acceptability and feasibility of using psychological and/or pharmacological interventions to treat mental health problems after complex traumatic events. l Research priorities: to identify candidate interventions that could feasibly be tested and used in the NHS and to make recommendations to the Health Technology Assessment programme about future research priorities.

Literature searches

Literature searches of the following databases were conducted: l Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCOhost (1937 onwards; search date: 20 April 2017). l Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane Library (from inception; search date: 21 April 2017). l EMBASE via Ovid (1974 to 2017 Week 16; search date: 19 April 2017). l International Pharmaceutical Abstracts via ProQuest (1970 onwards; search date: 30 August 2017).

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l MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE via Ovid (1946 to present; search date: 18 April 2017). l Published International Literature On Traumatic Stress (PILOTS) via ProQuest (1987 onwards; search date: 2 May 2017). l PsycINFO via Ovid (1806 to April Week 2 2017; search date: 18 April 2017). l Science Citation Index via Web of Science (1900 onwards; search date: 20 April 2017).

The full search strategies used are available in Appendix 1.

Inclusion and exclusion criteria

Population Neither DSM-IV nor ICD-10 distinguishes between PTSD and CPTSD. DSM-V does include a dissociative subtype, but it is unlikely that many studies have yet been conducted using this approach. ICD-11 criteria that will include CPTSD are not yet published and few studies will have used these criteria, making it difficult to identify studies using this diagnostic label. Our goal was therefore to identify studies based primarily on trauma history rather than diagnostic criteria.

We included adults > 18 years of age who had been exposed to complex interpersonal traumatic events, which were defined as follows:

. . . deliberate and premeditated event or series of events of an extreme and prolonged or repetitive nature that is experienced as extremely threatening or horrific and from which escape is difficult or impossible due to physical, psychological, maturational, family/environmental, or social constraints. Cloitre et al.10

This included (but was not limited to) adults exposed to childhood physical and/or sexual abuse, being a victim of or witnessing domestic violence, forcibly displaced persons (refugees, asylum seekers, internally displaced persons), torture survivors, those recruited into armed conflict as a child, those who had experienced ongoing armed conflict and combat, and those who had been relocated through human trafficking.

Studies were identified primarily based on trauma history rather than diagnostic criteria, and only those with adults > 18 years of age were included. The interpersonal trauma experience may have occurred at any age, but only studies of adults were included. Inclusion in the review was not restricted based on psychiatric comorbidities, with the exception of substance misuse disorders.

If studies included a mix of participants with complex interpersonal trauma history and single-event trauma history, studies were included if > 75% of participants had experienced complex interpersonal trauma (unless the data were presented separately).

Studies examining preventative therapies or interventions in populations not yet exhibiting psychological problems following complex traumatic events were excluded.

Interventions

Psychological interventions Studies that evaluated any first- or second-line psychological therapy aimed at improving symptoms (including comorbidities) of trauma- and stressor-related disorders delivered either to individuals or in a group were included. Complementary and alternative therapeutic interventions were excluded from

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this review. As per the protocol registered with PROSPERO34 and in keeping with the classification used by NICE,20 the following interventions were considered: l trauma-focused CBT that included one or more of the following types of treatment techniques: exposure, cognitive therapy, stress management l eye movement desensitisation and reprocessing (EMDR) l other psychological treatments used to treat trauma survivors and victims but that predominantly use non-CBT techniques: supportive therapy and non-directive counselling, psychodynamic therapies including interpersonal psychotherapy (IPT), hypnotherapy, mindfulness and compassion-focused therapies, acceptance and commitment therapies, accelerated resolution, and sensorimotor therapies.

A more detailed study categorisation was undertaken to better describe the volume of evidence (see Subgroup analyses: categorising interventions).

Where possible, analyses of group trauma-focused CBT and group non-trauma-focused CBT were considered, as planned. The approach used is detailed in Meta-regression analyses: predictors of treatment effectiveness. The volume of evidence permitted further superordinate categorisation (see Subgroup analyses: categorising interventions).

Pharmacological interventions All drug treatments subjected to experimental testing in the context of the treatment of mental health problems in people with a history of complex trauma were considered for inclusion. The following categories of pharmacotherapy were considered: selective serotonin reuptake inhibitors (SSRIs), antidepressants as a whole, antipsychotics, anticonvulsants and other medications typically used in the context of managing the symptoms of trauma and stressor disorders.

Comparators

Psychological interventions Psychological interventions were compared with the following: l waitlist l treatment as usual (defined as non-experimental active treatments that conform to best and/or clinical guideline recommended care and that are ordinarily made available to patients) l no intervention l symptom monitoring l repeated assessment or other minimal attention control group akin to psychological placebo l alternative psychological treatment l pharmacological treatment.

Pharmacological interventions Pharmacological interventions were compared with the following: l placebo l other medication l no intervention l psychological therapy.

Head-to-head comparisons Comparisons of two or more active interventions were included. Differences in comparators were taken into account during data summary and analyses. Network meta-analyses were conducted to provide comparisons of all interventions within a connected network (including comparisons of active interventions not originally evaluated in the included trials).

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 7 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. METHODS OF THE EFFECTIVENESS REVIEW AND META-ANALYSIS

Outcomes The outcomes measured were core symptoms related to trauma- and stressor-related disorders and outcomes associated with psychological and psychiatric comorbidities even in the absence of PTSD. However, all outcomes reported within studies were extracted to gain a comprehensive overview of all commonly reported outcomes.

Primary outcomes

l Reduction in severity of traumatic stress symptoms as measured using a validated and standardised clinician-rated scale. l Reduction in symptoms of difficulties with emotion regulation (e.g. Difficulties with Emotion Regulation Scale35) and interpersonal relationship problems (e.g. Inventory of Interpersonal Problems36).

Secondary outcomes

l Severity of self-reported traumatic stress symptoms using a standardised measure (e.g. Modified PTSD Symptom Scale37). l Reduction in depressive and/or anxiety symptoms measured using validated clinician-rated instruments (e.g. Hamilton Depression Rating Scale38) or validated patient self-reported instruments (e.g. Hospital Anxiety and Depression Scale39). l Reduction in symptoms of panic disorder. l Reduction in symptoms of disassociation. l Reduction in symptoms of functional somatic syndromes. l Reduction in substance misuse. l Acceptability measured in terms of intervention uptake, adherence and withdrawal (dropouts). l Adverse events and harms from trial data (e.g. worsening of traumatic stress symptoms). l Suicidal ideation, attempts and completion. l Functioning, disability and quality of life measured by validated clinician-rated scales (e.g. Global Assessment of Functioning) or validated self-reported scales (e.g. Short Form questionnaire-36 items). l Study designs. l RCTs and cluster RCTs (where relevant).

Because CPTSD and complex trauma make up an emerging and relatively new diagnostic category, we proposed to also identify and include non-randomised controlled studies so as to capture data on emerging treatments and treatments tested in more pragmatic settings that might not have been tested in the context of a RCT. Studies undertaken in any country and setting (i.e. both low and middle-income countries and high-income countries) were included. Single-group before-and-after studies, uncontrolled observational studies, single-subject designs, case studies, opinion papers, descriptive studies and editorials were excluded.

Study selection

The selection criteria and process were independently checked by an advisory group (see Advisory group). Three researchers (Julie Jones-Diette, Hollie Melton and Holly Dale) independently screened titles and abstracts. The EndNote library was split evenly between those involved in screening, but, to ensure the distribution was not weighted to any particular year or author groups, each reviewer screened a cross-section of the library across dates and authors. To ensure that the inclusion criteria were consistently applied, a 10% sample of records was first double screened based on the title and abstract by pairs of researchers. Consensus meetings with the rest of the research team were held at regular intervals to resolve unclear decisions at the title and abstract screening phase. Full-text records were similarly screened with consensus meetings used to resolve disagreements.

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Advisory group We convened a study advisory group that comprised the principal investigator (Peter Coventry) and co-investigator (Rachel Churchill), along with content and clinical experts in trauma studies, PTSD and CPTSD. The advisory group provided independent advice about the strategic direction and scientific and policy relevance of the research undertaken by the INCiTE (INterventions for Complex Traumatic Events) review team. The broad aim of the advisory group was to ensure that the INCiTE study met its objectives and to maximise the impact and benefit of the review to end-users. The chairperson of the advisory group shared with the INCiTE team search terms and preliminary results associated with an update of a review of treatments for PTSD. Our search was shared with the advisory group and vetted for accuracy and credibility. Following the first advisory group meeting, the INCiTE team was advised to modify the inclusion criteria to include populations with a history of complex traumatic events who also had psychosis. In addition, feedback from the clinical content experts suggested that screening decisions should include combat trauma of all kinds because of the increased likelihood that veterans who present with PTSD may have encountered other traumatic events prior to military service and that it is the experience of multiple forms of trauma resulting in symptoms associated with CPTSD.

Data extraction

Data extraction was piloted on a small sample of studies by three researchers independently. Both RCTs and non-RCTs were extracted using the same template and were managed in separate Microsoft Excel® (Microsoft Corporation, Redmond, WA, USA) spreadsheets. After consensus checking, the included records were split between three reviewers to singly extract, owing to the volume of evidence. Uncertainties were resolved by consultation between reviewers tasked with data extraction or by deferring to the wider review team. Extracted data across domains related to study and participant characteristics and outcomes were compiled in a spreadsheet. When they were presented, intention-to-treat data were extracted instead of complete cases.

If an included study was published across multiple manuscripts, we used the primary publication as the main source of information. New and follow-up data were taken from subsequent publications but the unit of allocation remained the study rather than numbers of publications.

Risk of bias

Randomised controlled studies of clinical effectiveness Studies were evenly distributed between researchers tasked with data extraction and each study was singly assessed for risk of bias. A subset of studies was used to pilot the Cochrane risk-of-bias tool. This tool assessed each study against domains known to be associated with bias in RCTs: selection, performance, detection, attrition, reporting and other biases (which were applied based on the specific context). Each study was assessed as being at ‘low’, ‘unclear’ or ‘high’ risk of bias across each of these domains. Attrition bias was used as an independent variable in the sensitivity analysis; this domain was checked by a further reviewer after all of the original appraisals had been made.

Selection bias was assessed by considering random sequence generation and allocation concealment; when these were not reported with sufficient detail, they were graded as at unclear risk. Performance bias considered the blinding of participants and personnel; when this was not possible owing to intervention type (e.g. comparing a psychological intervention with a waitlist), studies were graded as high risk. Detection bias was assessed by considering the blinding of outcomes assessors. The attrition bias domain took account of incomplete outcome data and how they were managed. When attrition was unequal, in high frequency or not appropriately managed by study authors, this was graded as high risk. Reporting bias was appraised by considering the risk of selective reporting. Generally, studies without a registered protocol were graded as being an unclear risk, while studies that favoured

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significant outcomes or obscured results were graded as high risk. Finally, other biases were assessed and descriptively reported if there were possible concerns not addressed by the existing domains of the tool.

Non-randomised controlled intervention studies Non-randomised controlled intervention studies that were subject to the same piloting and agreement process as RCTs were included. Two reviewers piloted the Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I),40 the Newcastle–Ottawa Scale41 and the NICE quality appraisal checklist.42 After piloting these tools, the pragmatic decision was taken to use a modified version of the NICE quality appraisal checklist42 used in public health guidance. There were few non-randomised controlled studies but the resources needed to use the ROBINS-I tool would have outstripped capacity in the team and compromised the schedule allocated for extracting data from the large volume of included RCTs.

Reviewers singly appraised the quality of each included non-randomised controlled intervention study. The checklist was originally developed based on the ‘Graphical Appraisal Tool for Epidemiological studies’ (GATE) tool43 and includes domains of population bias, allocation, outcomes and analyses, as well as summary judgements for internal and external validity. Ten items were not directly relevant to the included studies, so were graded as ‘not applicable’ (items 2.3, 2.5, 3.2, 3.4, 3.5, 3.6, 4.3, 4.5 and 4.6). Each study was graded ‘++’ indicating minimal risk of bias, ‘+’ indicating potential sources of bias or ‘–’ indicating significant sources of bias. The additional grade ‘NR’ was used when studies did not report information and ‘NA’ was used when an item was not applicable to the given study design.

Data analysis

Meta-analyses of clinical effectiveness and attrition Random-effects pairwise meta-analyses were conducted using Stata® 15 (StataCorp LP, College Station, TX, USA). We decided to use a frequentist approach for the pairwise meta-analyses, as this remains the standard approach in the literature.

Control conditions were grouped into two categories: controls (which included a waitlist or other controls with no or minimal therapeutic input) and active controls (including attention controls or treatment as usual with non-systematic psychological intervention input).

If multiple intervention groups were included in the study, we analysed the data in the following way:

l If one of the groups did not meet criteria for our review, we did not combine across groups but used data from the group that met our review criteria. l If studies included two intervention groups that met criteria for the same intervention classification, we combined them together. For example, if a study included a prolonged exposure group and a cognitive processing therapy group, we combined them together into one group for the trauma-focused CBT analyses. l However, of course, if a study included a mindfulness arm and a trauma-focused CBT arm, we did not combine them but included them in their appropriate subgroups.

Most outcomes were continuous. If all studies used the same scale, we calculated mean differences and their 95% confidence interval (CI). If studies used different scales to measure a particular outcome, we calculated standardised mean differences (SMDs) and their 95% CI. In keeping with established cut-off points of effect in behavioural medicine, SMDs of 0.56 to 1.2 were categorised as large, effect sizes of 0.33 to 0.55 were categorised as moderate and effect sizes ≤ 0.32 were categorised as small. For dichotomous outcomes, such as attrition, we calculated odds ratios (ORs) and their 95% CI.

Heterogeneity assessment was based on visual inspection of forest plots and the I2 statistic.44 A Q-value (approximating chi-squared distribution) of p < 0.1 indicated statistically significant heterogeneity.

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Statistical heterogeneity was explored using subgroup analyses, meta-regression and components network meta-analyses.

Subgroup analyses: categorising interventions Given the substantial and inherent heterogeneity expected from our broad research questions, we conducted a range of subgroup analyses.

First, we conducted meta-analyses including all psychological interventions versus controls or active controls in all populations.

Second, we grouped these meta-analyses of all psychological interventions into the following populations based on descriptions in the study and through discussion with clinical experts: veterans, people who had experienced childhood sexual abuse, refugees, people who had experienced domestic violence and war-affected civilians.

Third, we grouped the data according to intervention categories commonly reported in the literature based on reporting from the original papers and discussion with clinical experts: trauma-focused CBT, EMDR therapy, non-trauma-focused CBT, mindfulness, dialectical behaviour therapy (DBT) and IPT. We assessed the effectiveness of these intervention categories in the same populations as described above: all psychological interventions, veterans, childhood sexual abuse, refugees, domestic violence and war.

Fourth, we further grouped the data into three superordinate intervention categories:

1. single-component trauma-focused interventions: any trauma-focused intervention that includes a single therapeutic approach (e.g. trauma-focused CBT, EMDR) 2. multicomponent trauma-focused interventions: any intervention that is primarily trauma-focused but also includes elements of other theoretical approaches, such as mindfulness, present-centred therapy or counselling [e.g. Skills Training in Affect and Interpersonal Regulation (STAIR)] 3. single-component non-trauma-focused interventions: any non-trauma-focused intervention including a single theoretical approach (e.g. non-trauma-focused CBT, mindfulness, IPT, present-centred therapy).

These intervention categories were then grouped according to the populations listed above (i.e. all psychological interventions, veterans, childhood sexual abuse, refugees, domestic violence and war).

Meta-regression analyses: predictors of treatment effectiveness

Mixed-effects meta-regression analyses were conducted using the ‘metareg’ package in Stata 15 to examine the impact of differences in population and intervention components on the effectiveness of psychological interventions (using SMD as the outcome measure) for reducing trauma outcomes in all populations (number of trials = 46). We used a frequentist approach to supplement and compare with the more complex Bayesian approach used for the components network meta-analyses.

The impact of the following populations was explored based on the same categories described above for the subgroup analyses: veterans, people who had experienced childhood sexual abuse, refugees, people who had experienced domestic violence and war-affected civilians.

Intervention components were identified on the basis of study descriptions in the published manuscripts, accessing treatment manuals where available, and in discussion with clinical experts with experience of delivering these types of interventions. The following intervention components were included, as long as they had sufficient data to be included as covariates in the meta-regression: support, psychoeducation, relaxation, cognitive restructuring, in vivo exposure, imaginal exposure, virtual reality exposure, mindfulness and phased based.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 11 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. METHODS OF THE EFFECTIVENESS REVIEW AND META-ANALYSIS

We also assessed the impact of the following methods of intervention delivery on effectiveness: individual versus group, face to face versus other and duration of intervention (< 12 weeks, 12 weeks, > 12 weeks).

Components network meta-analyses

We sought to further explore the impact of different combinations of intervention components using network meta-analyses. We used a Bayesian approach, as this allows greater flexibility in fitting more complex models and, therefore, a more thorough exploration of heterogeneity.

As with the meta-regression analyses above, we began by conducting the component network meta-analyses using SMDs that combined different trauma outcomes and all populations. However, there were difficulties with compiling the model. Given the greater complexity of the network meta-analysis models, we judged that it would be appropriate to simplify the analyses by focusing on mean differences for the Clinician-Administered PTSD Scale (CAPS; i.e. the most frequently reported trauma outcome reporting scale; number of trials = 16) in all populations for this outcome.

We fitted models using WinBUGS 1.4.3 (MRC Biostatistics Unit, Cambridge, UK) based on the components network meta-analyses approach proposed by Welton et al.45 and an adaptation of the WinBUGS code reported in Freeman et al.46 All models used a normal likelihood for continuous outcomes and vague priors for treatment effect and between-trial standard deviation. Convergence was assessed based on visual assessment of trace plots, the Brooks–Gelman–Rubin statistic and autocorrelation plots using three Markov chain Monte Carlo methods. All models were judged to have reached convergence after 50,000 iterations. These iterations were then discarded and all results were based on a further 50,000 iterations.

Goodness of fit to the observed data was assessed using total residual deviance and the deviance information criterion (DIC). Total residual deviance approximately equal to the number of data points was considered to indicate acceptable fit.47 Greater than 5 points on the DIC was considered a substantial difference in goodness of fit between models.48

We compared four models:

1. Model 1 included the intervention categories used in the pairwise meta-analyses (trauma-focused CBT, EMDR, non-trauma-focused CBT, mindfulness and IPT) compared with either control or active control. 2. Model 2 included all intervention components originally assessed in the meta-regression analyses discussed above (support, psychoeducation, relaxation, cognitive restructuring, in vivo exposure, imaginal exposure, virtual reality exposure, mindfulness and phased based). In addition to these, it was also assumed that all active treatments and attention controls included a placebo component. We also took into account the effect of the control group (waitlist vs. active control). Each component had a separate effect and assumed the total effect of the intervention was a sum of these separate effects. 3. Model 3 included all intervention components in model 2 plus all available pairs of components. Seven pairs of intervention components were reported in two or more included studies and were therefore included in the analyses: support + psychoeducation, psychoeducation + relaxation, psychoeducation + cognitive restructuring, psychoeducation + imaginal exposure, relaxation + mindfulness, relaxation + cognitive restructuring and relaxation + imaginal exposure. This model allowed for interactions between pairs of interventions above or below what would be expected from the sum of their components. 4. Model 4 included all possible combinations of intervention components.

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Acceptability sensitivity analyses

For the attrition outcome, we were concerned that any differences between interventions and the control may be confounded by study design characteristics. Therefore, we conducted sensitivity analyses on attrition outcomes including only studies with a low risk of attrition bias and compared these findings with all included studies.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 13 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Chapter 3 Methods of the qualitative acceptability review

Objective

The aim of this element of the review was to identify, appraise and synthesise narratively qualitative data that addressed service user and provider perspectives about the acceptability and feasibility of using psychological and/or pharmacological interventions to treat mental health problems after complex traumatic events.

Literature searches

Literature searches of the following databases were conducted: CINAHL, EMBASE, MEDLINE and PsycINFO. The searches identified 4289 records, which were downloaded, imported into EndNote [Clarivate Analytics (formerly Thomson Reuters), Philadelphia, PA, USA] bibliographic software and de-duplicated to leave 1574 unique records. The full qualitative search strategy is available in Appendix 2.

Study selection

Qualitative research was defined as those studies that collected data using specific qualitative techniques such as unstructured interviews, semistructured interviews or focus groups, either as a stand-alone methodology or as a discrete part of a larger mixed-method study, and analysed qualitatively. Studies that collected data using qualitative methods but then analysed these data using quantitative methods were therefore excluded.

For qualitative evaluations, the inclusion criteria for population, intervention and comparisons were largely unchanged from those used to identify studies for the effectiveness syntheses. In addition, to ensure that we identified non-trial-based qualitative evaluations of acceptability of psychological and/or pharmacological interventions, we also included stand-alone studies not specifically linked to RCTs.

Population As per the effectiveness review.

Interventions As per the effectiveness review.

Comparators As per the effectiveness review.

Outcomes The outcomes were qualitative thematic and verbatim data related to service user and/or provider experiences of psychological and/or pharmacological interventions for mental health problems in the presence of complex trauma histories.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 15 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. METHODS OF THE QUALITATIVE ACCEPTABILITY REVIEW

Data extraction

The findings and supporting quotations from the nine qualitative studies included were extracted into a standardised template designed for the purpose of the review. For each study, the key themes, as reported by the study authors, were first categorised according to whether they addressed issues related to the ‘acceptability’ or ‘feasibility’ of interventions. Themes were then further coded into three subcategories: (1) uptake and adherence, (2) service experience and (3) professional competencies/ training. New thematic categories were created, where necessary, for any data that did not fit into the three main groupings.

Quality assessment

Following the lead established by the GRADE Working Group49 and the Cochrane Qualitative and Implementation Methods Group,50 we used the CERQual (certainty of the qualitative evidence) approach51 to assess both the methodological limitations of individual studies and the coherence of our review findings. CERQual assessment offers a framework to evaluate the certainty of evidence, addressing questions beyond the effectiveness of interventions, such as acceptability. Methodological limitations were assessed with the Critical Appraisal Skills Programme (CASP) checklist.52 The elements of the CASP assessment, questions 1 to 9, were assessed and scored as either ‘yes’, ‘no’ or ‘cannot say’. When a question was assessed as meeting the criteria describing a suitable methodological rigour, the question was scored as ‘yes’; conversely, if the methodology did not meet the expected level of methodological rigour or the information was not apparent from the methods, the study was scores as ‘no’ or ‘cannot say’,respectively. A ‘yes’ received a numeric score of 1.0, a ‘no’ scored 0 and ‘cannot say’ scored 0.5. Therefore, the maximum score, namely if each of the nine questions was allocated a ‘yes’ for methodological rigour, would be 9.0.

The coherence of the review was assessed by identifying patterns across the data that were contributed to by each of the individual included studies, for example by combining findings across multiple settings or different subgroups. The certainty of the evidence in each individual study was rated as ‘no concerns’, ‘minimal concerns’, ‘moderate concerns’ or ‘significant concerns’ by considering the CASP assessment and ranked according to the methodological limitations and coherence of each finding.

Data analysis

A narrative synthesis approach was used to summarise the research findings of the studies included. This approach allows the creation of a description and map of findings from the studies included for interpretation, but also allows the identification of both common and emergent themes (a thematic analysis) within and between studies. This methodology provides a broader perspective on solutions and recommendations that are relevant to end-users.

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Chapter 4 Results of the effectiveness review

Flow of the studies included

The searches identified 16,552 records, which were downloaded, imported into EndNote bibliographic software and de-duplicated to leave 10,212 unique records. In addition, 42 records were identified from International Pharmaceutical Abstracts. A total of 10,254 titles and/or abstracts were screened.

Approximately 10% of the titles and abstracts were pilot screened to achieve consistency and agreement between researchers. Full-text records were double screened at the following stage, and 328 were excluded for the reasons summarised in Figure 1.

Studies included

Overall, we included 105 papers, comprising 96 reports53–147 of RCTs (95 unique trials) and nine non-randomised trials.148–156 A table of the studies excluded, with rationale for their exclusion, can be found in Appendix 3.

Characteristics of the randomised controlled trials included Of the RCTs, the vast majority of trials were conducted in the USA (n = 6258–60,64,66,68–76,78,79,81,82,84,85,87,89–91, 93–95,97–102,104–107,109,110,112,115–117,120–133,135,137,140–142,146), followed by countries in Europe [Germany (n = 455,88,92,136), Denmark (n = 363,77,103,134), the Netherlands (n = 2138,139), Croatia (n = 180), Kosovo (n = 1143), Portugal (n = 183), Romania (n = 161) and Sweden (n = 1119)], countries in the Middle East [Iran (n = 456,57,111,118), Iraq/Iraqi

Records identified through database Additional records identified searching through other sources (quantitative n = 16,552) (n = 0)

Records after duplicates removed (quantitative n = 10,254)

Records screened Records excluded (n = 10,254) (n = 9493)

Full-text articles assessed Full-text articles excluded, for eligibility with reasons (n = 433) (n = 328) • Population, n = 112 • Intervention, n = 48 Studies included in • Comparator, n = 16 qualitative synthesis • Outcome(s), n = 12 (n = 105) • Study design, n = 86 • Conference abstract, n = 30 • Dissertation, n = 2 • Duplicate reference, n = 7 Studies included in • Language, n = 9 quantitative synthesis • Protocol, n = 4 (meta-analysis) • Letter, n = 1 (n = 79) • Retraction, n = 1

FIGURE 1 The PRISMA flow diagram indicating the flow of studies through the review process.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 17 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

Kurdistan (n = 362,144), Turkey/Syria (n = 353,54,65), Egypt (n = 1108)andIsrael(n = 1147)] and countries in Africa [Uganda (n = 2113,114), Burundi (n = 1145) and the Democratic Republic of the Congo (n = 186)]. One study took placeinSouthKorea67 and another took place remotely in Germany96 while its participants were located in Iraq. No studies were conducted in the UK. Appendix 3 details the comparisons in each study, as well as their characteristics.

In terms of the types of trauma that participants were exposed to, the vast majority of participants’ exposure related to their status as veterans (n = 47 studies56,58–60,64,65,67,71–74,78,80–85,88,91,94,95,97,99,102,104,105,107, 110–112,115,118,120–124,126,128–130,135,137,140,142,147), followed by refugees (n = 1753–55,63,87,89,90,108,113,114,116,119,133,134,136,138,139), those who experienced childhood sexual abuse (n = 1466,68–70,75–77,92,98,103,106,117,127,131,132,146), those who experienced war-related trauma (n = 1057,61,62,86,96,109,143–145), those who experienced mixed trauma (n = 379,93,141) and those who experienced domestic violence (n = 3100,101,125).

Of the 95 trials included, all trial arms with active interventions were categorised for analysis. For psychological interventions this included trauma-focused CBT (n = 4155,60–63,66,71,79,81,83,84,86,87,89,90,92–94,96,100,101, 105–107,109,113,114,117,119,124,126,128,136,140,143,144), EMDR (n = 1153,54,64,74,76,88,91,130,138,139), mindfulness (n = 757,95,115,120,121,142), non-trauma-focused CBT (n = 662,78,131,132,137), DBT (n = 469,70), other psychotherapy (n = 1293,103,106,114,120,124,125, 128,145,146), exposure only (n = 360,119,130)andIPT(n = 2,98,108 n = 2 for each non-trauma-focused non-CBT64,111 and stabilisation,138,139 and n = 1 for both biofeedback102 and other psychological interventions).142 Classen et al.68 conducted a trial in two interventions (trauma-focused therapy and psychotherapy) but presented combined results, so these were not included in the categorisation. The pharmacological interventions compared in the studies included were categorised as antidepressant (n = 15,59,65,67,73,82,112,116,118,133,141,147 of which 10 were SSRIs65,67,82,112,116,118,133,141,147), antipsychotic (n = 658,85,99,110,127,135) and anticonvulsant (n = 272,104), as well as prazosin (n = 384,122,123)andrivastigmine(n = 156). There were also a number of combined treatments: antidepressant and trauma-focused CBT (n = 6,63,97,116,134 of which there were three SSRI and trauma-focused CBT interventions63,116,134), SSRI and other psychotherapy (n = 263,80), antidepressant and other psychotherapy (n = 180), benzodiazepine and trauma-focused CBT (n = 1129) and d-cycloserine and trauma-focused CBT (n = 1129).

Psychological interventions were then grouped into superordinate classifications (as described in the methods), which were single-component trauma-focused (n = 4153–55,60–62,64,74,76,79,81,83,86,87,89–91,93,94,96,106,107, 109,113,114,117,119,124,126,128,136,138,139,144,145), single-component non-trauma-focused (n = 2757,62,64,78,95,98,106,108,111,114, 115,120,121,124,125,128,131,132,137–139,142,146), multicomponent trauma-focused (n = 1760,66,69–71,84,88,92,100,101,105,130,140, 143–145) and multicomponent non-trauma-focused (n = 470,93,103).

Characteristics of the non-randomised controlled trials included A total of nine non-RCTs were included in the review; eight compared psychological interventions with a control group148–153,155,156 and one compared a pharmacological intervention with placebo154 (see Appendix 6). Studies were conducted in a range of regions [Canada (n = 2152,156), Croatia (n = 1154), Germany (n = 1149), Iran (n = 1153), Israel (n = 1150), Palestine (n = 1155), Sweden (n = 1151) and the USA (n = 1148)], presenting a diverse selection of health-care systems that may differ from that in the UK. Studies were published between 1999152,153,156 and 2016,150 with one-third being published in 1999.

The population subgroups included in the non-RCTs were veterans (n = 3148,150,154), childhood sexual abuse (n = 3151,152,156), war affected (n = 2153,155) and refugees (n = 1149). When reported, the mean age of participants ranged from 30 to 60 years old. Across studies, there was largely equal representation of majority female149,151,152,156 and majority male populations.150,154,155 Further detail about the characteristics of populations of the studies included can be found in Appendix 7.

The majority of studies were compared with an inactive control (no intervention, waitlist or placebo), with the exception of two direct comparison studies,150,154 and effect sizes were not calculated for these.

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Another study included treatment as usual, which was considered to be an alternative active psychological intervention and so was narratively synthesised as a direct comparison.148 Intervention details are outlined in Appendix 4.

Quality of the studies included

Randomised controlled trials The quality of the RCTs included was assessed using the Cochrane Collaboration’s risk-of-bias tool, as described in Chapter 2, Randomised controlled studies of clinical effectiveness. The grading of each study across six domains can be found in Appendix 8.

Overall, reporting was quite variable, with a large proportion of responses being graded as ‘unclear’.Fiveof the six domains were largely assessed as being at an unclear or high risk of bias. This indicated that studies reported insufficient detail to make a clear decision about the risk of bias across these domains or, in most cases, that the study designs did not appropriately account for sources of bias. The exception to this was the domain of ‘other bias’, which was graded as a low risk of bias for over 80% of studies.

A small proportion of trials were rated as being at a high risk of selection bias. The majority of studies were unclear in reporting on selection bias (Figure 2). However, less than 20% were considered as at a low risk of bias based on allocation concealment and less than 50% were at a low risk based on random sequence generation.

Over half of the trials were rated as being at high risk of performance bias because the blinding of participants and personnel was inadequate or infeasible. The latter was especially true in the case of most psychological interventions, in which the nature of the allocated intervention could not easily be disguised.

Detection bias was generally considered as low risk or unclear for the majority of trials, with a slightly larger proportion being rated as unclear than low risk. This was indicative of the outcome assessment being blinded effectively or reported unclearly. Approximately 10% of studies were considered as being at high risk of detection bias.

In terms of attrition bias, gradings of low risk, high risk or unclear bias were almost equally prevalent across studies. This suggested that the majority of studies experienced high dropout and did not handle it appropriately or did not report sufficiently on the number of participants and withdrawals.

Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personnel (performance bias) Risk of bias Blinding of outcome assessment (detection bias) Low Unclear Incomplete outcome data (attrition bias) High Selective reporting (reporting bias) Other bias

0 25 50 75 100 Distribution (%)

FIGURE 2 Proportional distribution of the risk-of-bias grades across the RCTs included per domain of bias.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 19 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

Selective reporting was assessed via the reporting bias domain, for which a large majority of studies were graded as being unclear, typically owing to a lack of preregistration (see Figure 2). Close to 10% were considered as low risk in this domain of bias, and nearly 20% were considered as high risk.

Finally, there was generally a low risk of bias from other sources across the large majority of studies. The remainder of studies were graded as having an unclear risk of bias from sources not covered within the other domains. Just one study was graded as high risk from other sources of bias.100

Non-randomised controlled trials The quality of the nine non-randomised trials included was assessed using the NICE (2012)42 tool as described in Chapter 2, Methods, Non-randomised controlled intervention studies; the grading is presented in Table 1. Overall, methods were reported adequately to make summary judgements on studies. Notable exceptions were the availability of information to grade contamination (domain 2.6; present in only three studies148,152,156) and information regarding the similarity of other interventions across study arms (domain 2.7; clearly reported in four studies148,149,151,156).

Generally, population bias domains were well reported, with minimal or some potential sources of bias.

Allocation bias domains presented the largest subset of quality assessment and were also the most poorly reported. Investigator blinding (domain 2.4) was the highest risk domain, with a high risk of bias across all studies that reported sufficient detail to make a judgement.148,150–152,154,156

Outcome domains were also well reported, with most studies attaining a ‘+’ grading indicating some potential sources of bias, but not high risk.

Domains regarding analyses were mostly well reported, with baseline similarities between study arms (domain 4.1) and estimates of effect being given or calculable (domain 4.4), mostly showing low or some sources of bias.

Finally, summary grades of the overall risk of bias were mostly indicative of designs attempting to address sources of bias, with some potential risks. External validity showed minimal risk of bias; just one study was graded as high risk.153 By contrast, internal validity was not considered low risk in any study; three trials were judged to be high risk150,151,156 and one did not report sufficient detail.154

Meta-analyses of clinical effectiveness

Of the 104 RCTs and non-RCTs included in the systematic review, 79 included effectiveness data that could be meta-analysed.53–56,58,59,62,64–67,69,71–74,76,78,79,81,82,84–92,94–96,98–101,104–113,115,118,121–123,125–127,131,132,135,137–140,142–147 All of these studies were RCTs. We conducted a series of meta-analyses to investigate the effectiveness of psychological and pharmacological interventions on the primary outcome and, when the data permitted, a number of secondary outcomes. In summary, the comparisons that were meta-analysed were:

l psychological interventions versus control for all populations combined l psychological interventions versus control in veteran populations l psychological interventions versus control in war-affected populations l psychological interventions versus control in childhood sexual abuse populations l psychological interventions versus control in refugee populations l psychological interventions versus control in domestic violence populations l pharmacological interventions versus placebo in veteran and childhood sexual abuse populations.

NIHR Journals Library www.journalslibrary.nihr.ac.uk erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

TABLE 1 Risk-of-bias gradings for the non-randomised controlled studies included

Population bias Allocation

1.3: Do the 1.2: Is the eligible selected 2.1: Allocation 2.4: Were population or area participants or to intervention 2.2: Were participants or 2.8: Were all 1.1: Is the source representative areas represent (or comparison). interventions investigators 2.7: Were other participants population or of the source the eligible How was (and comparisons) blind to 2.6: Was interventions accounted source area well population or population or selection bias well described exposure and contamination similar in both for at study Authors (year) described? area? area? minimised? and appropriate? comparison? acceptably low? groups? conclusion?

King et al. (2013)148 ++ ++ + + ++ – ++ ++ ++

Levi et al. (2016)150 ++ ++ + – ++ – NR NR +

Morgan and ++ ++ – ++ NR ++

tal. et 152 Cummings (1999) 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Saxe and Johnson ++ ++++ – ++ – + (1999)156

Pivac et al. (2004)154 ++ NR NR + – NR NR NR

Lundqvist et al. ++ +–– –NR – + (2006)151

Salo et al. (2008)155 ++ + ++ – + NR NR NR –

Narimani et al. – ++++++NR NR NR – (2008)153

Kruse et al. (2009)149 ++ + ++ + ++ NR NR + –

continued o.2 o 43 No. 24 Vol. 21 22 EUT FTEEFCIEESREVIEW EFFECTIVENESS THE OF RESULTS IRJunl Library Journals NIHR www.journalslibrary.nihr.ac.uk

TABLE 1 Risk-of-bias gradings for the non-randomised controlled studies included (continued)

Allocation Outcomes Analyses Summary

4.1: Were 2.10: Did the exposure and intervention or comparison groups 4.4: Were the 5.1: Are the 5.2: Are the findings control comparison 3.3: Were all similar at baseline? 4.2: Was intention- estimates of study results generalisable to the reflect usual UK 3.1: Were outcome important outcomes If not, were these to-treat analysis effect size given internally valid source population Authors (year) practice? measures reliable? assessed? adjusted? conducted? or calculable? (i.e. unbiased)? (i.e. externally valid)?

King et al. (2013)148 NA ++ +++++++

Levi et al. (2016)150 NA ++ +++++– +

Morgan and NA + – +++++ Cummings (1999)152

Saxe and Johnson NA + – ++ – ++ – + (1999)156

Pivac et al. (2004)154 NA ++ +NR – NR +

Lundqvist et al. NA + – + – + – + (2006)151

Salo et al. (2008)155 ++ ++ ++ ––++ + ++

Narimani et al. ++ + + NR NR – + – (2008)153

Kruse et al. (2009)149 ++ ++ + ++ – ++ + ++ DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

When the data permitted, the following outcomes were meta-analysed: l PTSD symptoms l CPTSD symptoms

¢ emotional dysregulation ¢ interpersonal problems ¢ negative self-concept l depression symptoms l anxiety symptoms l quality of life l sleep quality.

All populations and trauma exposure combined

Post-traumatic stress disorder total symptoms A summary of meta-analyses of the effectiveness of psychological interventions across all populations for PTSD symptoms is shown in Appendix 9, Table 34. Overall, when all eligible trials were combined (39 trials, n = 2506)53–55,62,66,69,74,76,78,81,86,88,89,91,92,94–96,98,100,101,106–109,121,126,131,132,140,142–146,157–159 across all populations, psychological interventions were associated with a large and significant post-treatment effect in favour of a reduction in PTSD total symptoms (Figure 3).

Of the six trials (n = 259)71,84,87,113,137–139,160 that compared psychological interventions with an active control, the post-treatment effect size was smaller and in favour of a reduction in total PTSD symptoms, but not significantly (SMD –0.35, 95% CI –0.72 to 0.03; I2 = 47.0%). Ten trials (n = 738)78,81,92,95,98,121,132 measured outcomes after < 6 months and showed that psychological interventions were associated with a medium and significant effect in favour of a reduction in PTSD total symptoms (SMD –0.38, 95% CI –0.68 to –0.08; I2 = 79.4%).

When treatment effects were meta-analysed by intervention type, we showed that IPT was associated with the largest post-treatment effect on total PTSD symptoms (SMD –1.41, 95% CI –1.97 to –0.85; I2 = 0%). This result is based on two small studies (n = 66)98,108 and associated with a high degree of uncertainty, as indicated by the wide CIs for the individual and combined point estimates (see Appendix 10, Figure 27).

There was strong evidence from 21 trials (n = 1283)55,62,66,81,86,92,94–96,100,101,106,107,109,126,140,143,144,158,159 that trauma-focused CBT is effective for reducing PTSD total symptoms (see Appendix 10, Figure 28). Four trials (n = 206)81,87,92,113 that tested trauma-focused CBT measured outcomes at follow-up after < 6 months and were associated with a large and significant treatment effect (SMD –0.64, 95% CI –1.10 to –0.18; I2 = 44.9%). However, we did not find evidence of the effectiveness of trauma-focused CBT versus active controls.

Evidence from seven trials (n = 244)53,54,74,76,88,91,157 showed that EMDR was similarly effective at reducing PTSD symptoms post treatment (see Appendix 10, Figure 29). Two trials (n = 71)138,139 compared EMDR with an active control. Post-treatment effects were in favour of a small reduction in PTSD total symptoms, but this result was non-significant (SMD –0.15, 95% CI –0.62 to 0.32; I2 = 0%).

Mindfulness (three trials, n = 183)95,121,142 was associated with a small non-significant effect in favour of symptom reduction when compared with control post treatment (see Appendix 10, Figure 30). In two trials95,121 that measured outcomes at follow-up after < 6 months, mindfulness was not effective for PTSD symptoms (SMD –0.08, 95% CI –1.56 to –0.32; I2 = 59%).

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 23 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.70 (–2.56 to –0.84) 2.31 Acarturk (2016)54 37 33 –2.17 (–2.77 to –1.58) 2.74 Adenauer (2011)55 11 8 –1.88 (–2.99 to –0.77) 1.92 Bolton (2014)62 215 66 –0.33 (–0.61 to –0.05) 3.16 Carlson (1997)64 10 11 –0.94 (–1.85 to –0.04) 2.23 Chard (2005)66 36 37 –2.33 (–2.93 to –1.73) 2.73 Cloitre (2002)69 22 24 –1.30 (–1.93 to –0.66) 2.67 Devilly (1998)74 12 10 –0.03 (–0.87 to 0.81) 2.34 Edmond (1999)76 20 19 –1.09 (–1.77 to –0.42) 2.61 Engel (2015)78 29 29 0.13 (–0.38 to 0.65) 2.86 Franklin (2017)81 6 7 –1.05 (–2.22 to 0.13) 1.83 Hermenau (2013)86 15 15 –0.41 (–1.13 to 0.31) 2.53 Himmerich (2016)88 21 17 –0.47 (–1.12 to 0.18) 2.65 Hinton (2005)89 20 20 –2.17 (–2.96 to –1.38) 2.42 Hinton (2004)90 6 6 –2.40 (–3.94 to –0.85) 1.38 Jensen (1994)91 13 12 –1.00 (–1.84 to –0.17) 2.34 Jung (2013)92 14 14 –0.83 (–1.61 to –0.06) 2.45 Keane (1989)94 11 31 –0.24 (–0.93 to 0.45) 2.59 Kearney (2013)95 25 22 –0.50 (–1.08 to 0.08) 2.76 Knaevelsrud (2015)96 79 80 –0.92 (–1.25 to –0.59) 3.11 Krupnick (2008)98 32 16 –1.37 (–2.03 to –0.71) 2.63 Kubany (2003)100 18 14 –2.99 (–4.02 to –1.96) 2.04 Kubany (2004)101 45 40 –2.89 (–3.51 to –2.28) 2.71 Margolies (2011)105 15 12 –1.12 (–1.94 to –0.30) 2.37 McDonagh (2005)106 51 23 –0.62 (–1.12 to –0.12) 2.88 McLay (2011)107 10 9 –0.68 (–1.61 to 0.25) 2.20 Meffert (2014)108 10 8 –1.51 (–2.58 to –0.44) 1.98 Miyahira (2012)109 10 12 –0.50 (–1.35 to 0.35) 2.32 Possemato (2016)121 36 26 –0.05 (–0.55 to 0.45) 2.88 Reger (2016)126 30 47 –0.40 (–0.86 to 0.07) 2.94 Sikkema (2007)131 73 48 0.09 (–0.27 to 0.45) 3.07 Sikkema (2013)132 124 123 –0.03 (–0.28 to 0.22) 3.19 Ulmer (2011)140 12 9 –1.81 (–2.85 to –0.77) 2.03 Wahbeh (2016)142 52 25 –0.27 (–0.75 to 0.20) 2.92 Wang (2016)143 13 15 0.01 (–0.74 to 0.75) 2.50 Weiss (2015) trial 1: CETA144 99 50 –0.70 (–1.05 to –0.35) 3.09 Weiss (2015) trial 2: CPT144 124 64 –0.26 (–0.56 to 0.05) 3.14 Yeomans (2010)145 38 38 –0.28 (–0.73 to 0.17) 2.95 Zlotnick (1997)146 16 17 –0.85 (–1.57 to –0.14) 2.54 Overall (I2 = 85.3%; p = 0.000) –0.90 (–1.14 to –0.66) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 01 2 3 Favours intervention Favours control

FIGURE 3 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all psychological interventions with control. CETA, common elements treatment approach; CPT, cognitive processing therapy.

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Non-trauma-focused CBT (three trials, n = 548)62,78,131,132 was associated with small non-significant effects in favour of symptom reduction when compared with control post treatment (see Appendix 10, Figure 31). Treatment effects were also non-significant for non-trauma-focused CBT for PTSD outcomes in two trials78,132 that measured outcomes after < 6 months (SMD –0.02, 95% CI –0.25 to 0.20; I2 = 0%).

When interventions from 22 trials (n = 1191)53–55,62,66,74,76,81,86,89,91,92,94,96,100,101,106,107,109,126,144,157,158 were grouped using composite intervention categories, we showed that single-component and trauma- focused interventions based on a single theoretical approach were associated with a large and significant treatment effect in favour of a reduction in PTSD symptoms (see Appendix 10, Figure 32). A large effect was also observed in a meta-analysis of five trials (n = 276)54,78,81,95,98,132 that measured outcomes at follow-up after < 6 months (SMD –0.94, 95% CI –1.56 to –0.32; I2 = 77.6%).

Seven trials (n = 440)69,88,140,143–145,159 delivered multicomponent and trauma-focused interventions (DBT, EMDR, trauma-focused CBT and other psychotherapeutic approaches) and were associated with a large and significant effect in favour of a reduction in PTSD symptoms (see Appendix 10, Figure 32).

There was evidence (11 trials, n = 936)62,78,95,98,106,108,121,131,132,142,146 that single-component non-trauma- focused interventions (CBT, mindfulness, counselling, IPT and other psychotherapeutic approaches) were associated with a significant and moderate treatment effect in favour of a reduction in PTSD symptoms post treatment (see Appendix 10, Figure 34). In five trials (n = 462)78,95,98,121,132 that measured outcomes after < 6 months, the treatment effect for single-component non-trauma-focused interventions was small and non-significant (SMD –0.05, 95% CI –0.23 to 0.14; I2 = 0%). When compared with an active control (two trials, n = 62),137,160 single-component non-trauma-focused interventions were associated with a non-significant large treatment effect in favour of a reduction in PTSD symptoms (SMD –0.64, 95% CI –1.82 to 0.53; I2 = 76.9%).

Figure 4 shows the results of a meta-analysis that compared phase-based psychological interventions with control. Only six studies (n = 190)69,88,98,107,108,140 were coded as phased based for PTSD outcomes. The results show that a variety of trauma- and non-trauma-focused interventions (DBT, EMDR, IPT and trauma-focused CBT) are associated with a large and significant improvement in PTSD symptoms when delivered as part of a phase-based approach with a stabilisation component.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Cloitre (2002)69 22 24 –1.30 (–1.93 to –0.66) 21.72

Himmerich (2016)88 21 17 –0.47 (–1.12 to 0.18) 21.36

Krupnick (2008)98 32 16 –1.37 (–2.03 to –0.71) 20.87

McLay (2011)107 10 9 –0.68 (–1.61 to –0.25) 13.53

Meffert (2014)108 10 8 –1.51 (–2.58 to –0.44) 11.02

Ulmer (2011)140 12 9 –1.81 (–2.85 to –0.77) 11.49

Overall (I2 = 35.9%; p = 0.168) –1.13 (–1.54 to –0.73) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 4 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing phase-based psychological interventions with control.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 25 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

Complex post-traumatic stress disorder symptoms A summary of meta-analyses of the clinical effectiveness of psychological interventions across all populations for CPTSD symptoms is shown in Appendix 9, Table 35.

Emotional dysregulation Seven studies (n = 289)69,79,86,98,106,108,142 included data about symptoms of emotional dysregulation that could be meta-analysed across populations and trauma exposure. Figure 5 shows the results of a meta-analysis that compared all psychological interventions with control as regards a reduction in symptoms of emotional dysregulation at the end of treatment. The results favoured the interventions but did not reach statistical significance.

Of these seven trials, three compared trauma-focused CBT with control.79,86,106 At the end of treatment, trauma-focused CBT was associated with a small effect in favour of a reduction in symptoms of emotional dysregulation, but this result did not reach statistical significance (see Appendix 10, Figure 35). Two small studies (n = 51)79 that compared trauma-focused CBT with control measured outcomes after < 6 months and were associated with a medium but non-significant treatment effect (SMD –0.42, 95% CI –1.53 to 0.69; I2 = 72.3%).

Four studies (n = 163)98,106,108,142 compared single-component and non-trauma-focused interventions with control. At the end of treatment, the meta-analysis showed that single-component and non- trauma interventions were not significantly associated with a reduction in symptoms of emotional dysregulation (see Appendix 10, Figure 36).

The largest treatment effect for emotional dysregulation was associated with three studies (n = 112)69,98,108 that tested interventions that can be characterised as phased based. However, while the large treatment effect favoured a reduction in symptoms of emotional dysregulation, it was statistically non-significant (Figure 6).

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Cloitre (2002)69 22 24 –1.45 (–2.10 to –0.80) 14.82

Feske (2008)79 9 12 –1.02 (–1.95 to –0.10) 11.83

Hermenau (2013)86 15 15 0.11 (–0.61 to 0.83) 14.09

Krupnick (2008)98 32 16 0.09 (–0.51 to 0.69) 15.42

Meffert (2014)108 10 8 –0.97 (–1.96 to 0.02) 11.17

Wahbeh (2016)142 27 25 0.09 (–0.46 to 0.63) 16.05

McDonagh (2005)106 51 23 0.12 (–0.37 to 0.61) 16.62

Overall (I2 = 74.5%; p = 0.001) –0.38 (–0.88 to 0.12) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 5 Meta-analysis of post-treatment SMD for emotional dysregulation, comparing all psychological interventions with control.

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Cloitre (2002)69 22 24 –1.45 (–2.10 to –0.80) 34.85

Krupnick (2008)98 32 16 0.09 (–0.51 to 0.69) 35.62

Meffert (2014)108 10 8 –0.97 (–1.96 to 0.02) 29.52

Overall (I2 = 83.4%; p = 0.002) –0.76 (–1.79 to 0.27) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 6 Meta-analysis of post-treatment SMD for emotional dysregulation, comparing phase-based psychological interventions with control.

Negative self-concept Five studies (n = 215)92,100,101,125,142 included data about symptoms of negative self-concept that could be meta-analysed. Figure 7 shows the results of a meta-analysis that compared all psychological interventions with control as regards a reduction in symptoms of negative self-concept at the end of treatment. When combined, psychological interventions were associated with a large treatment effect in favour of a reduction in symptoms of negative self-concept, albeit with a high degree of uncertainty and heterogeneity.

Figure 37 (see Appendix 10) shows that, when only the trauma-focused CBT studies were meta-analysed (three trials, n = 145),92,100,101 the effect size was very large and significant but with high degree of uncertainty about the combined point estimate and high levels of heterogeneity (SMD 2.22, 95% CI 0.75 to 3.70; I2 = 90.4%).

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Jung (2013)92 14 14 0.76 (–0.01 to 1.53) 20.31

Kubany (2003)100 18 14 3.07 (2.03 to 4.12) 18.68

Kubany (2004)101 45 40 2.88 (2.27 to 3.49) 21.11

Reed (2006)125 10 10 1.81 (0.75 to 2.87) 18.60

Wahbeh (2016)142 25 25 0.64 (0.07 to 1.21) 21.30

Overall (I2 = 90.0%; p = 0.000) 1.81 (0.73 to 2.89) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 0 1 2 3 Favours control Favours intervention

FIGURE 7 Meta-analysis of post-treatment SMD for negative self-concept, comparing all psychological interventions with control (positive SMD equals improvement in symptoms).

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 27 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

A more homogeneous and significantly large treatment effect was associated with the two studies (n = 117)100,101 that were characterised as comparing multicomponent and trauma-focused interventions with control (SMD 2.93, 95% 2.40 to 3.45; I2 = 0%; see Appendix 10, Figure 38).

Single-component non-trauma-focused interventions (two studies; n = 70)125,142 were also associated with large and significant effects in favour of improvement in negative self-concept, but the overall point estimate had a high degree of uncertainty (SMD 1.14, 95% CI 0.01 to 2.27; I2 = 72.6%; see Appendix 10, Figure 39).

Interpersonal problems Only two studies (n = 94),69,98 both testing phase-based interventions, were identified that included outcome data for interpersonal problems that could be meta-analysed. The overall treatment effect was large and in favour of a reduction in symptoms associated with interpersonal problems, but did not reach significance (SMD –0.59, 95% CI –1.28 to 0.11; I2 = 61.9%; see Appendix 10, Figure 40).

Depression symptoms A summary of meta-analyses of the clinical effectiveness of psychological interventions across all populations for depression symptoms is shown in Appendix 9, Table 36. Figure 8 shows the results of the meta-analysis of the 31 studies (n = 1866)53–55,62,69,74,76,81,92,95,96,98,100,101,106,108,109,111,121,125,137,140,142,144,157–159 that compared all psychological interventions with control post treatment for depression symptoms. The results show that interventions were associated with a large effect in favour of a reduction in depression symptoms. When all psychological interventions were compared with control at follow-up after < 6 months, there was a medium and still significant effect in favour of a reduction in depression symptoms (SMD –0.51, 95% CI –0.80 to –0.22; I2 = 48%; nine trials, n = 410).54,78,81,87,92,95,98,111,121

When interventions were meta-analysed by type, studies that tested trauma-focused CBT were the most numerous. Fifteen studies (n = 1115)62,81,92,96,100,101,106,109,126,140,143,144,159 compared trauma-focused CBT with control post treatment. Figure 41 (see Appendix 10) shows that trauma-focused CBT was associated with a large and significant effect in favour of a reduction in depression symptoms. There was also a positive effect in the three studies (n = 104)81,87,92 that compared post-treatment outcomes at follow-up after < 6 months, although the point estimate was associated with considerable uncertainty (SMD –0.72, 95% CI –1.43 to –0.01; I2 = 56.6%).

Large and significant treatment effects in favour of a reduction of depression symptoms were also similarly observed in a meta-analysis (five trials, n = 182)53,54,74,76,157 that compared EMDR with control post treatment (see Appendix 10, Figure 42). In the two studies (n = 72)138,139 that compared EMDR with an active control, at the end of treatment the effect on depression symptoms favoured the intervention, but did not reach significance (SMD –0.32, 95% CI –1.23 to 0.59; I2 = 47.8%).

There was also some evidence from two small studies (n = 66)98,108 that IPT compared with control was effective at reducing symptoms of depression (see Appendix 10, Figure 43).

Three studies (n = 186),95,121,142 all of which included veteran populations, compared mindfulness with control post treatment. Mindfulness interventions were associated with a medium effect size in favour of a reduction in depression symptoms (see Appendix 10, Figure 44). In the two studies95,121 that measured outcomes at follow-up after < 6 months, mindfulness was also associated with a medium and significant treatment effect (SMD –0.41, 95% CI –0.79 to –0.02; I2 = 0%).

Non-trauma-focused interventions78,137 were not effective in reducing depression symptoms (see Appendix 10, Figure 45).

Using composite intervention categories, we showed that single-component and trauma-focused interventions (17 studies; n = 1034)53–55,62,74,76,81,92,96,100,101,106,109,126,144,157,158 based on a single theoretical

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

First author (year) Intervention Control ES (95% CI) Weight (%) (n) (n)

Acarturk (2015)53 15 14 –1.20 (–2.00 to –0.41) 3.05 Acarturk (2016)54 37 33 –1.74 (–2.29 to –1.18) 3.60 Adenauer (2011)55 11 8 –2.05 (–3.19 to –0.91) 2.34 Bolton (2014)62 215 66 –0.30 (–0.58 to –0.03) 4.10 Carlson (1997)64 10 11 –1.64 (–2.64 to –0.64) 2.61 Chard (2005)66 36 37 –2.00 (–2.57 to –1.44) 3.57 Cloitre (2002)69 22 24 –1.22 (–1.85 to –0.59) 3.42 Devilly (1998)74 13 10 –0.23 (–1.06 to –0.59) 2.98 Edmond (1999)76 20 19 –0.74 (–1.39 to –0.09) 3.38 Engel (2015)78 29 29 0.13 (–0.39 to 0.64) 3.68 Franklin (2017)81 6 7 –1.60 (–2.88 to –0.32) 2.09 Hinton (2004)90 6 6 –1.99 (–3.42 to –0.56) 1.85 Jung (2013)92 14 14 –0.49 (–1.25 to 0.26) 3.15 Kearney (2013)95 25 22 –0.62 (–1.21 to –0.03) 3.52 Knaevelsrud (2015)96 79 80 –1.03 (–1.36 to –0.70) 4.02 Krupnick (2008)98 32 16 –1.06 (–1.70 to –0.42) 3.41 Kubany (2003)100 18 14 –3.97 (–5.19 to –2.75) 2.19 Kubany (2004)101 45 40 –2.77 (–3.37 to –2.17) 3.50 Margolies (2011)105 14 9 –1.40 (–2.33 to –0.46) 2.74 McDonagh (2005)106 51 22 –0.62 (–1.13 to –0.11) 3.69 Meffert (2014)108 10 8 –1.46 (–2.52 to –0.40) 2.50 Miyahira (2012)109 10 12 0.09 (–0.75 to 0.93) 2.96 Moradi (2014)111 12 12 –0.72 (–1.55 to 0.11) 2.98 Possemato (2016)121 36 26 –0.28 (–0.78 to 0.23) 3.69 Reger (2016)126 30 46 –0.56 (–1.03 to –0.09) 3.77 Teng (2008)137 18 17 –0.33 (–0.99 to 0.34) 3.34 Ulmer (2011)140 12 9 –0.34 (–1.22 to 0.53) 2.89 Wahbeh (2016)142 52 25 –0.43 (–0.92 to 0.05) 3.74 Wang (2016)143 13 15 0.08 (–0.67 to 0.82) 3.17 Weiss (2015) trial 1: CETA144 99 50 –0.84 (–1.20 to –0.49) 3.99 Weiss (2015) trial 2: CPT144 124 64 –0.28 (–0.59 to 0.02) 4.07

Overall (I2 = 82.8%; p = 0.000) –0.94 (–1.20 to –0.68) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 012 3 Favours intervention Favours control

FIGURE 8 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all psychological interventions with control. CETA, common elements treatment approach; CPT, cognitive treatment therapy. approach were associated with a large and significant treatment effect in favour of a reduction in depression symptoms (see Appendix 10, Figure 46). A large and significant effect was also observed in the four studies (n = 174)53,81,87,92 that compared outcomes at follow-up after < 6 months (SMD –0.85, 95% –1.42 to –0.29; I2 = 62.5%).

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 29 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

Six studies (n = 340)69,140,143,144,159 compared multicomponent and trauma-focused interventions with control and were associated with a similarly large and significant effect in favour of a reduction in depression symptoms (see Appendix 10, Figure 47).

A smaller but still significant and favourable treatment effect was observed in the 10 studies (n = 594)62,78,95,98, 106,108,111,121,137,142 that compared single-component and non-trauma-focused interventions with control post treatment (see Appendix 10, Figure 48). There was a small and non-significant effect in the five studies (n = 236)78,95,98,111,121 that measured outcomes at follow-up after < 6 months (SMD –0.30, 95% –0.56 to 0.04; I2 = 0%).

Figure 9 shows that, post treatment, compared with control, phase-based interventions were associated with a large and significant treatment effect in favour of a reduction in depression symptoms, although this result is based on just four small studies.69,98,108,140

Anxiety symptoms A summary of meta-analyses of the clinical effectiveness of psychological interventions across all populations for anxiety symptoms is shown in Appendix 9, Table 37. Figure 10 shows the result of a meta-analysis of 13 studies (n = 1136)62,69,74,76,81,91,96,126,143,144,157 that compared all psychological interventions with control post treatment. Interventions were associated with a large and significant treatment effect in favour of a reduction in anxiety symptoms.

The majority of the studies (eight studies; n = 7)62,81,96,106,126,143,144 that included data about anxiety symptoms tested trauma-focused CBT. When compared with control post treatment, meta-analysis showed that trauma-focused CBT was associated with a large and significant effect in favour of a reduction in anxiety symptoms (Figure 11).

The largest effects in favour of a reduction in anxiety symptoms were observed in a meta-analysis of four studies (n = 102)74,76,91,157 that compared EMDR with control post treatment (see Appendix 10, Figure 49).

There were no data that could be meta-analysed that compared mindfulness or non-trauma-focused CBT with either control or an active control.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Cloitre (2002)69 22 24 –1.22 (–1.85 to –0.59) 33.94

Krupnick (2008)98 32 16 –1.06 (–1.70 to –0.42) 33.40

Meffert (2014)108 10 8 –1.46 (–2.52 to –0.40) 13.41

Ulmer (2011)140 12 9 –0.34 (–1.22 to 0.53) 19.25

Overall (I2 = 10.9%; p = 0.339) –1.03 (–1.43 to –0.63) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 00.5 1.0 Favours intervention Favours control

FIGURE 9 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing phase-based interventions with control.

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First author (year) Intervention Control ES (95% CI) Weight (%) (n) (n)

Bolton (2014)62 215 66 –0.19 (–0.46 to 0.09) 10.64

Carlson (1997)64 10 11 –1.39 (–2.36 to –0.43) 6.35

Cloitre (2002)69 22 24 –1.54 (–2.21 to –0.88) 8.27 Devilly (1998)74 13 10 –0.43 (–1.27 to 0.40) 7.13

Edmond (1999)76 20 19 –1.35 (–2.05 to –0.65) 8.02 Franklin (2017)81 6 7 –1.39 (–2.63 to –0.16) 4.95

Jensen (1994)91 11 8 –0.99 (–1.96 to –0.02) 6.32

Knaevelsrud (2015)96 79 80 –1.55 (–1.90 to –1.19) 10.24

Reger (2016)126 30 47 –0.14 (–0.59 to 0.32) 9.62

Wang (2016)143 13 15 0.06 (–0.68 to 0.80) 7.73

Weiss (2015) trial 1: CETA144 99 50 –0.98 (–1.34 to –0.62) 10.22 Weiss (2015) trial 2: CPT144 124 64 –0.33 (–0.63 to –0.03) 10.51

Overall (I2 = 83.4%; p = 0.000) –0.81 (–1.18 to –0.44) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 0 1 2 3 Favours intervention Favours control

FIGURE 10 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing all psychological interventions with control. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

First author (year) Intervention Control ES (95% CI) Weight (%) (n) (n)

Bolton (2014)62 101 66 –0.25 (–0.56 to 0.06) 14.56

Franklin (2017)81 6 7 –1.39 (–2.63 to –0.16) 6.50

Knaevelsrud (2015)96 79 80 –1.55 (–1.90 to –1.19) 14.20

McDonagh (2005)106 29 22 –0.43 (–0.99 to 0.13) 12.25

Reger (2016)126 30 47 –0.14 (–0.59 to 0.32) 13.26

Wang (2016)143 13 15 0.06 (–0.68 to 0.80) 10.44

Weiss (2015) trial 1: CETA144 99 50 –0.98 (–1.34 to –0.62) 14.17

Weiss (2015) trial 2: CPT144 124 64 –0.33 (–0.63 to –0.03) 14.62

Overall (I2 = 85.5%; p = 0.000) –0.60 (–1.01 to –0.19) 100.00

NOTE: weights are from random-effects analysis

– 3 – 2– 1013 2 Favours intervention Favours control

FIGURE 11 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing trauma-focused CBT with control. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 31 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

Using composite intervention categories, we showed in a meta-analysis that single-component and trauma-focused interventions (10 studies; n = 757)62,74,76,81,91,96,106,126,144,157 were associated with a large and significant treatment effect in favour of a reduction in anxiety symptoms (see Appendix 10, Figure 50).

Compared with control, multicomponent and trauma-focused interventions were associated with the largest treatment effect in favour of a reduction of anxiety symptoms (SMD –0.85, 95% CI –1.60 to –0.10; I2 = 80.4%).69,143,144 This meta-analysis included studies that tested a phase-based intervention and trauma-focused CBT (see Appendix 10, Figure 51).

Only two studies (n = 225)62,106 compared single-component and non-trauma-focused interventions with control post treatment: one tested a counselling intervention and one tested non-trauma-focused CBT. Although the treatment effect favoured a reduction in anxiety symptoms, the effect was small and did not reach significance (see Appendix 10, Figure 52).

Quality of life A summary of meta-analyses of the clinical effectiveness of psychological interventions across all populations for quality of life is shown in Appendix 9, Table 38. We identified five trials (n = 307)95,96,106,109,143 that included quality-of-life data that could be meta-analysed. Figure 12 shows the result of a meta-analysis that compared all psychological interventions with control post treatment.

Four of these five studies (n = 260)96,106,109,143 compared trauma-focused CBT with control post treatment. Although interventions favoured a small improvement in quality of life, the effect size did not reach significance (SMD 0.23, 95% CI –0.33 to 0.79; I2 = 73.9%; see Appendix 10, Figure 53).

Sleep quality A summary of meta-analyses of the clinical effectiveness of psychological interventions across all populations for sleep quality is shown in Appendix 9, Table 39. Only three studies (n = 111)140,142,159 included data about sleep quality that could be meta-analysed. When compared with control post treatment, all psychological interventions were associated with a large and significant effect on sleep

First author (year) Intervention Control ES (95% CI) Weight (n) (n) (%)

Kearney (2013)95 25 22 0.38 (–0.19 to 0.96) 20.34

Knaevelsrud (2015)96 79 80 0.84 (0.51 to 1.16) 27.16

McDonagh (2005)106 29 23 0.14 (–0.40 to 0.69) 21.14

Miyahira (2012)109 10 12 –0.23 (–1.08 to 0.61) 14.43

Wang (2016)143 12 15 –0.12 (–0.84 to 0.60) 16.93

Overall (I2 = 65.5%; p = 0.021) 0.28 (–0.15 to 0.71) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours control Favours intervention

FIGURE 12 Meta-analysis of post-treatment effect size (ES) for quality of life, comparing all psychological interventions with control (positive ES favours intervention).

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quality (SMD –1.00, 95% CI –1.49 to –0.51; I2 = 28.8%; see Appendix 10, Figure 54). A larger and significant treatment effect in favour of improved sleep quality was observed in a meta-analysis of just two small studies140,159 that compared trauma-focused CBT with control post treatment (SMD –1.30, 95% CI –1.87 to –0.73; I2 = 0%; see Appendix 10, Figure 55).

Psychological interventions versus control A summary of all of the clinical effectiveness meta-analyses undertaken within each trauma exposure can be found in Appendix 9.

Veterans A summary of meta-analyses of the clinical effectiveness of psychological interventions in veterans for PTSD, depression and anxiety symptoms is shown in Appendix 9, Table 40. Twenty-three trials were identified that included data about veteran populations. Five trials were not included in the meta-analysis: three compared head-to-head interventions,120,124,128 one compared trauma-focused CBT with exposure alone60 and one did not include extractable data.83

Post-traumatic stress disorder symptoms Figure 13 shows the result of a meta-analysis (14 trials, n = 502)74,78,81,88,91,94,95,107,121,126,140,142,157,159 that compared all psychological interventions with control post treatment. The medium treatment effect favours a significant reduction in PTSD symptoms.

Four trials (n = 180)78,95,121 measured PTSD outcomes at follow-up after < 6 months and, while psychological interventions were associated with a small treatment effect in favour of interventions, this did not reach significance (SMD –0.20, 95% –0.72 to 0.33; I2 = 63.1%).

First author (year) Intervention Control SMD (95% CI) Weight (%) (n) (n)

Carlson (1997)64 10 11 –0.94 (–1.85 to –0.04) 5.06 Devilly (1998)74 12 10 –0.03 (–0.87 to 0.81) 5.65 Engel (2015)78 29 29 0.13 (–0.38 to 0.65) 9.91 Franklin (2017)81 6 7 –1.05 (–2.22 to 0.13) 3.40 Himmerich (2016)88 21 17 –0.47 (–1.12 to 0.18) 7.83 Jensen (1994)91 13 12 –1.00 (–1.84 to –0.17) 5.67 Keane (1989)94 11 31 –0.24 (–0.93 to 0.45) 7.28 Kearney (2013)95 25 22 –0.50 (–1.08 to 0.08) 8.80 Margolies (2011)105 15 12 –1.12 (–1.94 to –0.30) 5.83 McLay (2011)107 10 9 –0.68 (–1.61 to 0.25) 4.89 Possemato (2016)121 36 26 –0.05 (–0.55 to 0.45) 10.10 Reger (2016)126 30 47 –0.40 (–0.86 to 0.07) 10.88 Ulmer (2011)140 12 9 –1.81 (–2.85 to –0.77) 4.13 Wahbeh (2016)142 52 25 –0.27 (–0.75 to 0.20) 10.57

Overall (I2 = 41.7%; p = 0.051) –0.48 (–0.72 to –0.24) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 13 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing all psychological interventions with control in veteran populations.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 33 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

Six trials (n = 106)81,94,100,107,126,159 compared trauma-focused CBT with control post treatment. Trauma- focused CBT was associated with a large and significant treatment effect in favour of a reduction in PTSD total symptoms (SMD –0.77, 95% CI –1.20 to –0.33; I2 = 44.6%; see Appendix 10, Figure 56).

A meta-analysis of four trials (n = 106)74,88,91,157 showed that EMDR was associated with a smaller but still significant treatment effect when compared with control post treatment (see Appendix 10, Figure 57).

Studies that included veterans95,121,142 provided all of the data in the previous meta-analysis that compared mindfulness with control post treatment and at follow-up after < 6months(seeAppendix 10, Figure 58).

No studies that included veterans compared non-trauma-focused CBT with either a control or an active control group.

Figure 59 (see Appendix 10) shows the results of a meta-analysis (seven trials, n = 219)74,81,91,94,107,157 that compared single-component and trauma-focused interventions with control post treatment. This shows that single-component and trauma-focused interventions were associated with a medium and significant effect in favour of a reduction in PTSD symptoms. The size of the effect was about half that observed in the equivalent analysis for all populations and trauma exposures pooled.

The largest effect was observed in a meta-analysis of three small studies (n = 86)88,140,159 that compared multicomponent and trauma-focused interventions with control post treatment (see Appendix 10, Figure 60).

Single-component and non-trauma-focused interventions were not associated with a significant treatment effect in favour of a reduction in PTSD symptoms post treatment in veterans (see Appendix 10, Figure 61).78,95,121,142

Four trials compared psychological interventions with active control (sleep and nightmare management, placebo and psychoeducation).71,84,137,160 It was unclear if psychological interventions as a whole (SMD –0.44, 95% CI –0.98 to 0.10; I2 = 64%; four trials, n = 188) or trauma-focused CBT (SMD –0.26, 95% CI –0.88 to 0.35; I2 = 51.1%; two trials, n = 126) were effective for PTSD symptoms.

Depression Figure 14 shows the results of a meta-analysis (11 trials; 445)74,78,81,95,111,121,126,137,140,142,157,159 that compared all psychological interventions with control post treatment. The size of the treatment effect is smaller than the effect observed in the equivalent analysis that pooled PTSD outcomes across all populations and trauma exposures. In five studies (n = 201)78,81,95,111,121 that measured outcomes at follow-up after < 6 months, all psychological interventions were associated with a medium effect in favour of a reduction in depression symptoms, but this effect was not significant (SMD –0.38, 95% CI –0.78 to 0.01; I2 = 42.3%).

When only those studies that compared trauma-focused CBT with control post treatment were considered, the meta-analysis (three trials, n = 112)81,126,159 showed that interventions were associated with a large and significant treatment effect in favour of a reduction of depression symptoms (see Appendix 10, Figure 62). There was, however, no evidence of a significant difference between trauma- focused CBT and active control (SMD –0.04, 95% CI –0.55 to 0.48; I2 = 38.7%; two trials, n = 128).71,84

Compared with control post treatment, EMDR was similarly associated with large effects in favour of a reduction in depression symptoms, but the overall point estimate was non-significant and associated with considerable uncertainty (see Appendix 10, Figure 63).74,157

The pooled population meta-analysis that compared mindfulness with control post treatment and after < 6 months included only studies with veterans and is shown in Appendix 10, Figure 64.95,121,142

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

First author (year) Intervention Control SMD (95% CI) Weight (%) (n) (n)

Carlson (1997)64 10 11 –1.64 (–2.64 to –0.64) 5.75

Devilly (1998)74 13 10 –0.23 (–1.06 to 0.59) 7.47

Engel (2015)78 29 29 0.13 (–0.39 to 0.64) 12.33

Franklin (2017)81 6 7 –1.60 (–2.88 to –0.32) 3.95

Kearney (2013)95 25 22 –0.62 (–1.21 to –0.03) 10.98

Margolies (2011)105 14 9 –1.40 (–2.33 to –0.46) 6.32

Moradi (2014)111 12 12 –0.72 (–1.55 to 0.11) 7.47

Possemato (2016)121 36 26 –0.28 (–0.78 to 0.23) 12.49

Reger (2016)126 30 46 –0.56 (–1.03 to –0.09) 13.27

Ulmer (2011)140 12 9 –0.34 (–1.22 to 0.53) 6.99

Wahbeh (2016)142 52 25 –0.43 (–0.92 to 0.05) 12.99

Overall (I2 = 46.8%; p = 0.043) –0.56 (–0.84 to –0.28) 100.00

NOTE: weights are from random-effects analysis

–1.0 –0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 14 Meta-analysis of post-treatment SMD for total depression symptoms, comparing all psychological interventions with control in veteran populations.

No studies that included veteran populations compared non-trauma-focused CBT with control for depression symptoms.

Single-component and trauma-focused interventions were associated with large and significant effects in favour of a reduction in depression symptoms (see Appendix 10, Figure 65).74,81,126,157

There was less evidence in favour of multicomponent and trauma-focused interventions, which were not significantly associated with a reduction in depression symptoms in a meta-analysis that included only two small trials (see Appendix 10, Figure 66).140,159

By contrast, a meta-analysis that included five studies (n = 268)78,95,111,121,142 that compared single- component and non-trauma-focused interventions showed that interventions were associated with a medium but significant effect in favour of a reduction in depression symptoms (see Appendix 10, Figure 67). Four of these studies (n = 188)78,95,111,121 measured outcomes after < 6 months, but the effect was not significant (SMD –0.27, 95% CI –0.56 to 0.02; I2 = 0%).

Anxiety There was less evidence for using psychological interventions for managing anxiety symptoms than other symptoms in veteran populations. We identified five studies (n = 153)74,81,91,126,157 that showed, in a meta- analysis, that overall, when pooled together, psychological interventions compared with control were associated with a large and significant effect in favour of a reduction in anxiety symptoms (Figure 15).

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 35 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

First author (year) Intervention Control SMD (95% CI) Weight (%) (n) (n)

Carlson (1997)64 10 11 –1.39 (–2.36 to –0.43) 17.82

Devilly (1998)74 13 10 –0.43 (–1.27 to 0.40) 20.61

Franklin (2017)81 6 7 –1.39 (–2.63 to –0.16) 13.23

Jensen (1994)91 11 8 –0.99 (–1.96 to –0.02) 17.72

Reger (2016)126 30 47 –0.14 (–0.59 to 0.32) 30.61

Overall (I2 = 54.0%; p = 0.069) –0.74 (–1.29 to –0.18) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 15 Meta-analysis of post-treatment SMD for total anxiety symptoms, comparing all psychological interventions with control in veteran populations.

Only two studies (n = 90)81,126 compared trauma-focused CBT with control post treatment in veterans. Meta-analysis showed that interventions favoured a reduction in anxiety symptoms, but this effect was not significant and was associated with a high degree of uncertainty (see Appendix 10, Figure 68).

By contrast, EMDR compared with control was associated in a meta-analysis (three trials, n = 63)74,91,157 with a large treatment effect in favour of a reduction in anxiety symptoms post treatment (see Appendix 10, Figure 69). The size of this effect was marginally smaller than that observed in the meta-analysis that pooled all populations and that included more studies.

War-affected populations A summary of meta-analyses of the clinical effectiveness of psychological interventions across war-affected populations for PTSD, depression and anxiety symptoms is shown in Appendix 9, Table 41. Ten studies that included war-affected populations were identified; eight were included in the meta-analyses. Azad Marzabadi and Hashemi Zadeh57 did not report outcomes that were sufficiently similar to other studies (i.e. they only reported on the WHO Quality of Life questionnaire) and Bichescu et al.61 compared head-to-head interventions; therefore, these were not meta-analysed.

Post-traumatic stress disorder total symptoms Figure 16 shows the results of a meta-analysis that compared all psychological interventions (eight trials, n = 933)62,86,96,109,143–145 with control post treatment. The results show that psychological interventions were associated with a medium effect size in favour of a reduction in total PTSD symptoms. The size of this effect was comparable to that observed for veteran populations.

The majority of the studies (seven trials, n = 743)62,86,96,109,143,144 in war-affected populations compared trauma-focused CBT with control post treatment. Figure 70 (see Appendix 10) shows that trauma- focused interventions were associated with a medium and significant effect in favour of reducing PTSD symptoms in war-affected populations.

A very similar result was found when single-component and trauma-focused interventions were compared in a meta-analysis (five trials, n = 566)62,86,96,109,144 with control post treatment (SMD –0.51, 95% CI –0.80 to –0.23; I2 = 55.9%).

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

First author (year) Intervention Control ES (95% CI) Weight (%) (n) (n)

Bolton (2014)62 215 66 –0.33 (–0.61 to –0.05) 18.85

Hermenau (2013)86 15 15 –0.41 (–1.13 to 0.31) 6.68

Knaevelsrud (2015)96 79 80 –0.92 (–1.25 to –0.59) 16.79

Miyahira (2012)109 10 12 –0.50 (–1.35 to 0.35) 5.16

Wang (2016)143 13 15 0.01 (–0.74 to 0.75) 6.42

Weiss (2015) trial 1: CETA144 99 50 –0.70 (–1.05 to –0.35) 15.92

Weiss (2015) trial 2: CPT144 124 64 –0.26 (–0.56 to 0.05) 17.78

Yeomans (2010)145 38 38 –0.28 (–0.73 to 0.17) 12.41

Overall (I2 = 50.4%; p = 0.049) –0.46 (–0.68 to –0.25) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 16 Meta-analysis of post-treatment effect size (ES) for total PTSD symptoms, comparing all psychological interventions with control in war-affected populations. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

Three studies delivered therapies as part of a multicomponent and trauma-focused intervention.143–145 When meta-analysed, these three studies (n = 253) showed that multicomponent and trauma-focused interventions were associated with a medium effect size in favour of a reduction in PTSD symptoms post treatment, but the overall point estimate was more uncertain than in the other meta-analyses in this population subgroup (see Appendix 10, Figure 71).

Depression symptoms Six trials (n = 827)62,96,109,143,144 were identified that included data that could be meta-analysed for depression symptoms in the war-affected subgroup. All of these studies compared trauma-focused CBT with control post treatment. When meta-analysed together, Figure 17 shows that trauma-focused CBT is associated with a medium and significant effect size in favour of a reduction in depression symptoms.

When trauma-focused CBT was delivered as part of a single-component intervention and compared with control, the meta-analysis (four trials, n = 536)62,96,109,144 shows that the intervention was associated with a similarly medium and significant effect size in favour of a reduction in depression symptoms (see Appendix 10, Figure 72). However, in the two studies that tested trauma-focused CBT as part of a multicomponent intervention, the meta-analysis (n = 177)143,144 shows that the treatment effect favoured a reduction in depression symptoms but did not reach significance (see Appendix 10, Figure 73).

Anxiety symptoms Five trials (n = 691)62,96,143,144 were identified that included data that could be meta-analysed for depression symptoms in the war-affected subgroup. All of these studies compared trauma-focused CBT with control post treatment. When meta-analysed together, Figure 18 shows that trauma-focused CBT is associated with a large and significant effect size in favour of a reduction in anxiety symptoms.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 37 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

First author (year) Intervention Control ES (95% CI) Weight (n) (n) (%)

Bolton (2014)62 101 66 –0.38 (–0.69 to –0.06) 20.11

Knaevelsrud (2015)96 79 80 –1.03 (–1.36 to –0.70) 19.69

Miyahira (2012)109 10 12 0.09 (–0.75 to 0.93) 9.62

Wang (2016)143 13 15 0.08 (–0.67 to 0.82) 11.08

Weiss (2015) trial 1: CETA144 99 50 –0.84 (–1.20 to –0.49) 19.18

Weiss (2015) trial 2: CPT144 124 64 –0.28 (–0.59 to 0.02) 20.33

Overall (I2 = 74.8%; p = 0.001) –0.48 (–0.82 to –0.15) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 17 Meta-analysis of post-treatment effect size (ES) for total depression symptoms, comparing all trauma-focused CBT interventions with control in war-affected populations. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

First author (year) Intervention Control ES (95% CI) Weight (n) (n) (%)

Bolton (2014)62 101 66 –0.25 (–0.56 to 0.06) 21.22

Knaevelsrud (2015)96 79 80 –1.55 (–1.90 to –1.19) 20.79

Wang (2016)143 13 15 0.06 (–0.68 to 0.80) 15.94

Weiss (2015) trial 1: CETA144 99 50 –0.98 (–1.34 to –0.62) 20.75

Weiss (2015) trial 2: CPT144 124 64 –0.33 (–0.63 to –0.03) 21.30

Overall (I2 = 90.4%; p = 0.000) –0.64 (–1.18 to –0.10) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 18 Meta-analysis of post-treatment effect size (ES) for total anxiety symptoms, comparing trauma-focused CBT with control in war-affected populations. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

When trauma-focused CBT was delivered as part of a single-component intervention and compared with control, the meta-analysis (three trials, n = 514)62,96,144 shows that the intervention was associated with a large effect size in favour of a reduction in anxiety symptoms, but this effect did not reach significance (see Appendix 10, Figure 74). Similarly, in the two studies143,144 that tested trauma-focused CBT as part of a multicomponent intervention, the meta-analysis (n = 177) shows that the treatment effect favoured a reduction in depression symptoms but did not reach significance and was associated with considerable uncertainty (see Appendix 10, Figure 75).

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Childhood sexual abuse A summary of meta-analyses of the clinical effectiveness of psychological interventions across populations exposed to childhood sexual abuse for PTSD, depression and anxiety symptoms is shown in Appendix 9, Table 42. Thirteen of these studies included data that could be meta-analysed in the childhood sexual abuse subgroup; nine studies (n = 687)66,69,76,92,98,106,131,132,146 were included in the meta-analyses. Those excluded from the meta-analyses were Cloitre et al.,69 which was a deconstruction trial; Lau and Kristensen,103 which compared analytic with systemic group therapy; Classen et al.,68 which combined data from trauma-focused CBT and present-centred therapy groups, making it difficult to separate out and interpret the intervention effects; and Owens et al.,117 which only reported loss of PTSD diagnosis (an outcome not reported in any other study in this population).

Post-traumatic stress disorder total symptoms Figure 19 shows the results of a meta-analysis (nine trials, n = 687)66,69,76,92,98,106,131,132,146 that compared all psychological interventions with control post treatment. The treatment effect was large and significant and about twice the size of the comparable result in the meta-analysis that assessed the effectiveness of all psychological interventions across all populations. Three studies (n = 323)92,98,132 measured outcomes at follow-up after < 6 months. The meta-analysis of these three studies showed that the treatment effect still favoured a reduction in PTSD symptoms, but it did not reach significance (SMD –0.27, 95% CI –0.71 to 0.17; I2 = 53.6%).

Three studies (n = 153)66,92,106 compared trauma-focused CBT with control post treatment. The meta-analysis shows that trauma-focused CBT was the most effective intervention in this subgroup. Figure 76 (see Appendix 10) shows that this intervention was associated with a large effect in favour of a reduction in PTSD symptoms, but the wide CIs suggest that this result is particularly uncertain.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Chard (2005)66 36 37 –2.33 (–2.93 to –1.73) 11.06

Cloitre (2002)69 22 24 –1.30 (–1.93 to –0.66) 10.84

Edmond (1999)76 20 19 –1.09 (–1.77 to –0.42) 10.64

Jung (2013)92 14 14 –0.83 (–1.61 to –0.06) 10.09

Krupnick (2008)98 32 16 –1.37 (–2.03 to –0.71) 10.71

McDonagh (2005)106 51 23 –0.62 (–1.12 to –0.12) 11.54

Sikkema (2007)131 73 48 0.09 (–0.27 to 0.45) 12.15

Sikkema (2013)132 124 123 –0.03 (–0.28 to 0.22) 12.54

Zlotnick (1997)146 16 17 –0.85 (–1.57 to –0.14) 10.42

Overall (I2 = 89.6%; p = 0.000) –0.90 (–1.43 to –0.37) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 19 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing all psychological interventions with control in childhood sexual abuse populations.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 39 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

By contrast, non-trauma-focused CBT, meta-analysed in two studies (n = 368),131,132 did not favour the intervention when compared with control post treatment (see Appendix 10, Figure 77).

When studies (three trials, n = 119)66,76,92,106 were grouped using the composite categories, we showed that single-component and trauma-focused interventions were associated with a large and significant effect in favour of a reduction in PTSD symptoms (see Appendix 10, Figure 78).

Larger and significant effects in favour of a reduction in PTSD symptoms were observed in the meta- analysis that compared multicomponent and trauma-focused interventions with control post treatment, but the treatment estimate was associated with considerable uncertainty (SMD –1.82, 95% CI –2.83 to –0.81; I2 = 81.3%; two trials, n = 122). Single-component and non-trauma-focused interventions (five trials, n = 494)98,106,131,132,146 were shown, in a meta-analysis, to be associated with a medium and significant effect that favoured a reduction in PTSD symptoms (see Appendix 10, Figure 79). This analysis included a phase-based study of IPT that was associated with a large and significant effect.98 Two of these trials measured outcomes at follow-up after < 6 months and a meta-analysis shows that there was no significant difference between interventions and control (SMD –0.08, 95% CI –0.31 to 0.15; I2 = 0%).98,132

Depression Figure 20 shows the result of a meta-analysis (six trials, n = 307)69,76,92,98,106 that compared all psychological interventions with control post treatment. Psychological interventions were associated with a large and significant effect in favour of a reduction in depression symptoms.

Two of these six trials measured outcomes at follow-up after < 6 months; the treatment effect still favoured interventions and was significant (SMD –0.52, 95% CI –0.99 to –0.04; I2 = 0%).92,98

Figure 80 (see Appendix 10) shows that trauma-focused CBT, when compared with control post treatment, is associated with a large but non-significant effect size in favour of a reduction in depression symptoms. This analysis was based on three small studies (n = 152) and there is considerable uncertainty regarding the overall point estimate.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Chard (2005)66 36 37 –2.00 (–2.57 to –1.44) 17.62

Cloitre (2002)69 55 24 –1.22 (–1.85 to –0.59) 16.53

Edmond (1999)76 20 19 –0.74 (–1.39 to –0.09) 16.25

Jung (2013)92 14 14 –0.49 (–1.25 to 0.26) 14.65

Krupnick (2008)98 32 16 –1.06 (–1.70 to –0.42) 16.44

McDonagh (2005)106 51 22 –0.62 (–1.13 to –0.11) 18.51

Overall (I2 = 70.5%; p = 0.005) –1.04 (–1.50 to –0.57) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 20 Meta-analysis of post-treatment SMD for depression symptoms, comparing all psychological interventions with control in childhood sexual abuse populations.

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

There was some tentative evidence from a meta-analysis of three studies (n = 118)76,92,106 that single- component and trauma-focused interventions were similarly associated with a large and significant effect size (see Appendix 10, Figure 81).

Single-component and non-trauma-focused interventions were associated with a medium and significant effect in favour of a reduction in depression symptoms in this subgroup (see Appendix 10, Figure 82). This analysis was based on three small studies (n = 118).76,92,106

Larger and significant effects in favour of a reduction in depression symptoms were observed in the meta-analysis that compared multicomponent and trauma-focused interventions with control post treatment, but the treatment estimate was associated with considerable uncertainty (SMD –1.63, 95% CI –2.40 to –0.85; I2 = 69.7%; two trials, n = 122).

Anxiety symptoms Only two studies (n = 90)76,106 included anxiety outcome data that could be meta-analysed. Figure 83 (see Appendix 10) shows that single-component and trauma-focused interventions (one testing EMDR, one testing trauma-focused CBT) are associated with a large effect in favour of a reduction in anxiety symptoms, but the effect did not reach significance.

Refugee populations A summary of meta-analyses of the clinical effectiveness of psychological interventions across refugee populations for PTSD, depression and anxiety symptoms is shown in Appendix 9, Table 43. Twelve studies that included refugee populations were identified; however, few meta-analyses were possible. The following trials did not appear in any meta-analyses: l Neuner et al.114 compared trauma-focused CBT, supportive counselling and psychoeducation and there was no comparison with a control group. l Paunovic and Ost119 compared trauma-focused CBT with an exposure-only intervention. l In Stenmark et al.,136 trauma-focused CBT data were not extractable.

Post-traumatic stress disorder symptoms Figure 21 shows the results of a meta-analysis (six trials, n = 188)53–55,89,108,136,158 that compared all psychological interventions with control post treatment. Interventions were associated with a very large and significant effect size in favour of a reduction in PTSD symptoms. Three studies (n = 235)54,87,113 measured outcomes at follow-up after < 6 months and, in the meta-analysis, the treatment effect was large and significant at follow-up (SMD –0.66, 95% CI –1.22 to –0.09; I2 = 72.7%).

Three small studies (n = 71)55,89,158 compared trauma-focused CBT with control post treatment and were associated in a meta-analysis with a very large and significant treatment effect in favour of a reduction in PTSD symptoms (see Appendix 10, Figure 83). Two larger studies (n = 165)87,113 that compared trauma-focused CBT with control measured outcomes at follow-up after < 6 months. The meta-analysis of these two studies showed that the treatment effect favoured interventions but did not reach significance (SMD –0.40, 95% CI –0.87 to 0.06; I2 = 86.3%).

There was some evidence, based on two small trials (n = 99),53,54 that EMDR, when compared with control post treatment, was effective at reducing total PTSD symptoms (see Appendix 10, Figure 85).

A large and significant effect in favour of a reduction in total PTSD symptoms was observed in a meta-analysis (five trials, n = 170)53–55,89,158 that compared single-component and trauma-focused interventions with control post treatment (see Appendix 10, Figure 86). Two studies (n = 133)54,87 measured outcomes at follow-up after < 6 months and, in a meta-analysis, the treatment effect favoured the interventions but did not reach significance (SMD –0.67, 95CI% –1.65 to 0.32; I2 = 86.3%).

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 41 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. RESULTS OF THE EFFECTIVENESS REVIEW

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.70 (–2.56 to –0.84) 16.27

Acarturk (2016)54 37 33 –1.74 (–2.29 to –1.18) 39.21

Adenauer (2011)55 11 8 –1.88 (–2.99 to –0.77) 9.74

Hinton (2005)89 20 20 –2.17 (–2.96 to –1.38) 19.25

Hinton (2004)90 6 6 –2.40 (–3.94 to –0.85) 5.02

Meffert (2014)108 10 8 –1.51 (–2.58 to –0.44) 10.51

Overall (I2 = 0.0%; p = 0.879) –1.84 (–2.18 to –1.49) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 21 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing all psychological interventions with control in refugee populations.

In addition to the comparisons with control, two studies (n = 71)138,139 compared EMDR with stabilisation only. There was insufficient evidence to conclude that EMDR was more effective post treatment (SMD –0.15, 95% CI –0.62 to 0.32; I2 = 0%) and at follow-up after < 6 months (SMD –0.15, 95% CI –0.80 to 0.49; I2 = 22.4%).

Depression symptoms Figure 22 shows the results of a meta-analysis (five trials, n = 148)53–55,108,158 that compared all psychological interventions with control post treatment. There is evidence that psychological interventions are effective in reducing symptoms of depression in refugee populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.20 (–2.00 to –0.41) 21.99

Acarturk (2016)54 37 33 –1.57 (–2.11 to –1.03) 48.06

Adenauer (2011)55 11 8 –2.05 (–3.19 to –0.91) 10.70

Hinton (2004)90 6 6 –1.99 (–3.42 to –0.56) 6.82

Meffert (2014)108 10 8 –1.46 (–2.52 to –0.40) 12.43

Overall (I2 = 0.0%; p = 0.764) –1.56 (–1.93 to –1.18) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 22 Meta-analysis of post-treatment SMD for depression symptoms, comparing all psychological interventions with control in refugee populations.

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There was only modest evidence from a meta-analysis of two small trials (n = 31)55,158 that trauma-focused CBT when compared with control is associated with large and significant treatment effects in favour of a reductionindepressionsymptoms;thewide CIs suggest this result is uncertain (see Appendix 10, Figure 87). Two other trials (n = 133)54,87 measured outcomes at follow-up after < 6 months and a meta-analysis shows that the treatment effect favoured interventions but did not reach significance (SMD –0.73, 95% CI –1.57 to 0.10; I2 = 81.3%).

Evidence to support the use of EMDR for managing depression in this population was also based only on data from two small trials (n = 99).53,54 When compared with control post treatment, EMDR was associated with a large and significant treatment effect in favour of a reduction in depression symptoms (see Appendix 10, Figure 88).

Taken together, single-component and trauma-focused interventions that included trauma-focused CBT and EMDR were effective at reducing depression in refugee populations. A meta-analysis (four trials, n = 130)53–55,158 showed that, overall, these interventions are associated with a large and significant treatment effect (see Appendix 10, Figure 89).

Two studies also compared EMDR with stabilisation only.138,139 There was insufficient evidence to conclude that EMDR was more effective post treatment (SMD –0.32, 95% CI –1.23 to 0.59; I2 = 47.8%; two trials, n = 72) or at follow-up after < 6 months (SMD –0.01, 95% CI –0.47 to 0.45; I2 = 0%; two trials, n = 73).

Anxiety symptoms Only data from two studies that compared EMDR with stabilisation included data on anxiety symptoms that could be extracted.138,139 There was no evidence that EMDR was effective in reducing anxiety symptoms in refugee populations post treatment (SMD –0.36, 95% CI –0.82 to 0.11; I2 = 0%; two trials, n = 73) or at follow-up after < 6months(SMD–0.43, 95% CI –1.21 to 0.35; I2 = 35.1%; two trials, n = 73).

Domestic violence A summary of meta-analyses of the clinical effectiveness of psychological interventions across populations exposed to domestic violence for PTSD, depression and anxiety symptoms is shown in Appendix 9, Table 44.

Post-traumatic stress disorder symptoms Three trials were identified that measured PTSD symptoms in populations affected by domestic violence. Two of the three trials were included in the meta-analyses that compared trauma-focused CBT with control post treatment and interventions were associated with a large and significant treatment effect (SMD –2.92, 95% CI –3.45 to –2.39; I2 = 0%; two trials, n = 117).100,101

The other trial in this subgroup compared forgiveness therapy with an alternative treatment including anger validation, assertiveness and interpersonal skills training and could not be meta-analysed.125

Depression symptoms The same two trials that compared trauma-focused CBT with control also reported post-treatment outcomes for depression. A meta-analysis showed that interventions were associated with a large and significant treatment effect, but there is a high degree of uncertainty about the overall point estimate (SMD –3.24, 95% CI –4.40 to –2.09; I2 = 66.6%; two trials, n = 117).125

Pharmacological interventions versus placebo Nineteen trials were identified that compared pharmacological interventions with placebo. Rezaei Ardani et al.56 tested rivastigmine augmentation and this study was not included in the meta-analyses because there were no other comparable interventions to combine it with. Two other studies were excluded from the meta-analyses because they compared head-to-head interventions, with no placebo

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group.65,67 All the trials (n = 16)58,59,72,73,82,84,85,99,104,110,112,118,122,123,135,147 included in the meta-analyses, except one trial in childhood sexual abuse, were in veteran populations.

Total post-traumatic stress disorder symptoms A summary of meta-analyses of the clinical effectiveness of pharmacological interventions for PTSD symptoms is shown in Appendix 9, Table 45. A meta-analysis of six trials (n = 338)59,73,82,112,118,147 compared antidepressants with placebo post treatment. The results show that there was a medium treatment effect in favour of antidepressants, but this did not reach significance (see Appendix 10, Figure 90).

Four trials (n = 293)82,112,118,147 were included in a meta-analysis that compared SSRIs with placebo. Figure 91 (see Appendix 10) shows that SSRIs were associated with a large effect in favour of a reduction in total PTSD symptoms, but this did not reach significance.

Data about the effectiveness of antipsychotics were meta-analysed in five trials (n = 365).58,85,99,110,135 Antipsychotics were associated with a medium and significant treatment effect in favour of a reduction in total PTSD symptoms post treatment (see Appendix 10, Figure 92).

Only two trials that compared anticonvulsants with placebo were meta-analysed and there was little evidence that these classes of drugs were effective at reducing total PTSD symptoms (see Appendix 10, Figure 93).72,104

Three trials (n = 110) compared prazosin with placebo and a meta-analysis showed that this sympatholytic medication is associated with a medium treatment effect post treatment in favour of reducing total PTSD symptoms (see Appendix 10, Figure 94).84,122,123

Depression symptoms A summary of meta-analyses of the clinical effectiveness of pharmacological interventions for depression symptoms is shown in Appendix 9, Table 46. Antidepressant medication was compared with placebo post treatment in a meta-analysis that included three trials (n = 220).59,73,82 The results were inconclusive, with no evidence that these classes of drugs were effective in reducing depression symptoms in veteran populations (see Appendix 10, Figure 95).

There was some evidence drawn from two trials (n = 266)99,135 that antipsychotic medication compared with placebo post treatment favoured the intervention, but the treatment effect did not reach significance (see Appendix 10, Figure 96).

There was very little evidence that anticonvulsants compared with placebo post treatment were effective in reducing depression symptoms. A meta-analysis of two trials (n = 106)72,104 showed that the treatment effect marginally favoured the placebo group (see Appendix 10, Figure 97).

In a meta-analysis of two trials (n = 76)84,123 that compared prazosin with placebo post treatment, the treatment effect favoured prazosin but did not reach significance.

There were insufficient data to assess the effectiveness of SSRIs. Only one study that compared SSRIs with placebo reported a depression outcome.82 Among the other studies that tested SSRIs, one study did not report depression outcomes separately and instead presented combined depression and anxiety data using the Hospital Anxiety and Depression Scale total,112 and two other trials did not report any depression outcome data.118,147

Anxiety symptoms No meta-analyses were possible for anxiety outcomes.

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Psychosis symptoms A summary of meta-analyses of the clinical effectiveness of pharmacological interventions for psychosis symptoms is shown in Appendix 9, Table 47. All of the trials included in the meta-analyses that compared antipsychotic medication with placebo tested risperidone. Three trials were identified that included post-treatment outcome data related to symptoms of psychosis; all used the Positive and Negative Syndrome Scale (PANSS).58,85,99

There was no good evidence that antipsychotic medication reduces symptoms of psychosis in veteran and childhood sexual abuse populations.

In a meta-analysis of three trials (n = 329),58,85,99 risperidone was associated with a reduction in positive psychotic symptoms on the PANSS, but the treatment effect did not reach significance and the overall point estimate was very uncertain (see Appendix 10, Figure 98).

In a meta-analysis of one small and one medium-sized trial, the treatment effect did not favour risperidone for either negative or total scores on the PANSS, although the effects were not significant (see Appendix 10, Figures 99 and 100).85,99 In the same meta-analysis, there was some evidence that risperidone favoured an improvement on the general psychopathology scale of the PANSS, but the effect did not reach significance (see Appendix 10, Figure 101).

Sleep quality A summary of meta-analyses of the clinical effectiveness of pharmacological interventions for sleep quality is shown in Appendix 8, Figure 26. Prazosin was the only pharmacological intervention with sufficient data to conduct meta-analyses; it was more effective than placebo (mean difference –2.53, 95% CI –3.82 to 1.23; I2 = 0%; three trials, n = 109).84,122,123

Meta-analysis of attrition

Of the RCTs included, 46 studies representing 47 trials in psychological interventions reported attrition data.53,55,62,64,66,69,71,76,78,79,81,83,84,86–92,94–96,98,100,105–109,111,115,121,125,126,128,131,132,135–140,144,145 Thirteen RCTs reported attrition data for pharmacological interventions.56,58,72,73,82,84,85,99,104,110,118,127,141 We conducted meta-analyses to investigate the odds of attrition from psychological and pharmacological interventions. Owing to a subset of trials reporting zero attrition, ORs were not calculable for eight trials;88–91,94,111,125,138 therefore, these were excluded from the analyses presented. The comparisons meta-analysed for odds of attrition from psychological interventions were considered two ways:

1. psychological interventions versus control for all populations combined, reported by intervention category 2. all psychological interventions versus control, reported by trauma experience.

All pharmacological interventions included in this analysis were in veteran populations, with the exception of one study in individuals with a history of childhood sexual abuse;127 therefore, veterans-only pharmacological intervention attrition meta-analyses were undertaken (see Veterans).

Intervention categories

Trauma-focused cognitive–behavioural therapy Twenty-one studies (n = 1557)55,62,66,79,81,83,86,87,92,96,100,105–107,109,126,128,136,140,144 reported attrition figures in trauma-focused CBT across all populations, and indicated participation in a trauma-focused CBT intervention was significantly associated with a reduction in the odds of dropout compared with controls (Figure 23).

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First author (year) Intervention Control OR (95% CI) Weight (%) (n) (n)

Adenauer (2011)55 16 18 2.75 (0.67 to 11.24) 5.66 Bolton (2014)62 101 66 0.35 (0.16 to 0.77) 9.33 Chard (2005)66 36 35 1.04 (0.34 to 3.16) 7.21 Feske (2008)79 13 14 0.38 (0.06 to 2.52) 3.84 Franklin (2017)81 19 8 0.04 (0.00 to 0.70) 1.88 Gamito (2010)83 7 3 0.62 (0.02 to 19.58) 1.46 Hermenau (2013)86 19 19 0.18 (0.01 to 4.00) 1.76 Hijazi (2014)87 41 22 0.93 (0.08 to 10.85) 2.60 Jung (2013)92 17 17 1.00 (0.17 to 5.83) 4.27 Knaevelsrud (2015)96 79 80 1.03 (0.55 to 1.94) 10.44 Kubany (2003)100 19 18 5.14 (0.52 to 51.29) 2.89 Margolies (2013)105 20 20 171 (0.40 to 7.34) 5.45 McDonagh (2005)106 51 23 0.40 (0.10 to 1.55) 5.88 McLay (2011)107 10 10 3.32 (0.12 to 91.60) 1.57 Miyahira (2012)109 29 13 0.21 (0.05 to 0.94) 5.31 Reger (2016)126 108 54 0.20 (0.08 to 0.48) 8.70 Resick (2015)128 56 52 043 (0.16 to 1.15) 7.96 Stenmark (2013)136 51 30 0.79 (0.30 to 2.07) 8.11 Ulmer (2011)140 12 9 0.10 (0.00 to 2.13) 1.80 Weiss (2015) trial 1: 99 50 0.39 (0.02 to 8.20) 1.81 CETA144 0.04 (0.00 to 0.62) 2.08 Weiss (2015) trial 2: 129 64 CPT144 0.57 (0.36 to 0.88) 100.00 Overall (I2 = 44.1%; p = 0.016)

NOTE: weights are from random-effects analysis

0.1 0.2 0.3 0.51.02.03.05.0 10.0 Favours intervention Favours control

FIGURE 23 Meta-analysis of ORs of attrition for trauma-focused CBT interventions compared with control. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

Four trials stood out owing to ORs that favoured increased attrition from the intervention; these had smaller sample sizes (< 20 participants per arm) and did not have a common trauma population (including veterans,105,107 domestic violence populations100 and refugees55).

Eye movement desensitisation and reprocessing Few controlled EMDR trials reported attrition data (three trials, n = 179).53,64,76 All favoured increased odds of attrition in the intervention group, with a non-significant pooled estimate suggesting uncertainty (OR 1.79, 95% CI 0.79 to 4.07; I2 = 0.0%). Trials included within this analysis were each from different populations (refugees,53 veterans64 and those with a history of childhood sexual abuse76).

Mindfulness There were also few mindfulness trials reporting attrition (three trials, n = 141).57,95,121 The pooled estimate suggested that the odds of attrition of individuals in mindfulness interventions were one-third those of individuals on a waitlist, but this finding did not reach significance (OR 0.29, 95% CI 0.05 to 1.74; n = 141). There was also moderate heterogeneity in the sample with the CI including 1, suggesting mindfulness interventions could also have greater odds of attrition than waitlists.

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Non-trauma-focused cognitive–behavioural therapy There were insufficient data comparing non-trauma-focused CBT with an inactive control to perform analyses.

Trauma populations Meta-analyses were carried out according to each intervention category within populations in which there were multiple studies present. The results for each of these can be found in Appendix 10. The following sections give the results of attrition from any psychological intervention within each population and highlight notable contrasts due to the sparsity of data in grouped meta-analyses.

Veterans Twelve trials (n = 616)66,78,81,83,95,105–107,109,121,128,157 were included in this meta-analysis, which compared psychological intervention with a control (see Appendix 10, Figure 102). Veterans receiving any psychological intervention had less than half the odds of attrition as those on a waitlist (OR 0.49, 95% CI 0.26 to 0.92; I2 = 41.8%), a statistically significant result. This suggests that it is likely that psychological therapies experience favourable dropout in comparison with waitlists or non-interventions in veteran populations.

Four trials (n = 225) compared psychological interventions with an active control71,84,115,137 and also showed reduced attrition among veterans receiving psychological intervention (OR 0.34, 95% CI 0.17 to 0.68; I2 = 0.0%; see Appendix 10, Figure 103).

Pharmacological interventions A sufficient number of pharmacological trials in veterans reported attrition to analyse the odds of dropout in antidepressant intervention, including three studies of SSRIs82,118,141 (OR 0.56, 95% CI 0.29 to 1.07; I2 = 24.9%; four studies, n = 345; see Appendix 10, Figure 104)73,82,118,141 and antipsychotics (OR 0.46, 95% CI 0.14 to 1.56; I2 = 56.5%; four studies, n = 414; see Appendix 10, Figure 105).58,85,99,110 Two studies reported attrition for the use of anticonvulsants72,104 (see Appendix 10, Figure 106).

Although all had an OR that favoured reduced attrition in the intervention group, none was significant.

Childhood sexual abuse Based on five trials (n = 414),69,92,98,131,140 individuals with experience of childhood sexual abuse and receiving psychological therapy had almost one-quarter the odds of dropout as inactive controls (OR 0.24, 95% CI 0.08 to 0.75; I2 = 26.5%; see Appendix 10, Figure 107). Three of the five studies in the analysis were also phased based.69,98,140

One trial reported attrition data for a pharmacological intervention, comparing antipsychotics with placebo; therefore, an OR was not calculated for these data.127

Refugee populations Evidence for attrition in refugee populations was mixed. Five studies (n = 298)53,55,87,108,136 were associated with psychological intervention having greater odds of attrition than controls, a finding that was not significant (OR 1.21, 95% CI 0.69 to 2.12; I2 = 0.0%; see Appendix 10, Figure 108). Across trials, odds were not consistent in favouring increased or decreased odds of attrition, resulting in a wide CI for the pooled estimate.

Domestic violence There were only two studies on psychological interventions for individuals exposed to domestic violence.62,100 Both investigated individual therapies and they had opposing directions of effect for attrition (see Appendix 10, Figure 109).

War-affected populations Six trials of psychological interventions gave a pooled OR that suggested reduced attrition for psychological intervention (when compared with inactive controls) in war-related trauma populations (OR 0.66, 95% CI

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0.27 to 1.60; I2 = 36.7%; n = 695).57,86,96,144,145 However, the CI includes 1, while an equivalent number of trials favour both reduced and increased odds of attrition. There is large uncertainty as regards the direction of effect, despite low to moderate heterogeneity (see Appendix 10, Figure 110).

Meta-regression analyses: predictors of treatment effectiveness

We conducted meta-regression analyses for any validated trauma outcome measure (using SMDs) and in all populations.

Model 1: predictors of treatment effectiveness by population type Table 2 shows the results of the univariable analyses. Interventions delivered in studies that included veterans were less likely to be effective than interventions delivered in studies in other populations. In addition, interventions delivered in studies that included people who had experienced domestic violence were more effective than studies that included other populations. However, there were few studies of people exposed to domestic violence and therefore it is unclear if further studies will consistently show greater effectiveness for people who have experienced domestic violence.

In multivariable analyses both remained statistically significant: studies of veterans [coefficient 0.41, standard error (SE) 0.20; p = 0.049] and studies of people experiencing domestic violence (coefficient

–2.01, SE 0.51; p < 0.001). The multivariable model was statistically significant [F2,42 = 11.51; p < 0.001) and explained some of the heterogeneity (adjusted R2 = 38.96%); however, a substantial proportion of heterogeneity remained unexplained (I2 residual = 79%).

Model 2: predictors of treatment effectiveness by intervention components When covariates for intervention content were assessed, only imaginal exposure was found to have a statistically significant association with effectiveness, but psychoeducation had a borderline statistically significant effect (Table 3). Therefore, both covariates were included in the multivariable analysis; psychoeducation was no longer statistically significant (coefficient –0.39, SE 0.23; p = 0.1) and imaginal exposure was borderline statistically significant (coefficient –0.44, SE 0.24; p = 0.07). The multivariable

model as a whole was statistically significant (F2,42 = 3.88; p = 0.03) and explained some of the heterogeneity (adjusted R2 = 15.78%), but a substantial proportion of heterogeneity remained unexplained (I2 residual = 81.19%).

Model 3: treatment effectiveness by delivery method Studies that tested individually delivered interventions reported improved outcomes compared with studies that tested interventions delivered in a group (Table 4). Since almost all interventions were delivered face to face, it was not possible to confirm if there was a difference in effectiveness compared with other modalities. There was no evidence that the duration of intervention had an impact on effectiveness.

TABLE 2 Predictors of effectiveness of psychological interventions by population type (univariable analyses)

Populations Coefficient (standard error) p-value

Veterans 0.56 (0.23) 0.02 Childhood sexual abuse –0.04 (0.30) 0.89

Refugees –0.36 (0.28) 0.21

Domestic violence –2.19 (0.52) < 0.001

War affected 0.25 (0.45) 0.59

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TABLE 3 Univariable predictors of treatment effectiveness by intervention component

Components Coefficient (SE) p-value

Support –0.12 (0.33) 0.71

Psychoeducation –0.47 (0.23) 0.052

Relaxation –0.06 (0.27) 0.83

Mindfulness –0.13 (0.36) 0.73

Cognitive –0.03 (0.25) 0.91

In vivo exposure –0.04 (0.45) 0.92 Virtual reality exposure 0.36 (0.49) 0.47

Imaginal exposure –0.51 (0.24) 0.04

Phased based –0.36 (0.37) 0.33

TABLE 4 Predictors of treatment effectiveness by delivery method

Delivery method Coefficient (SE) p-value

Face to face vs. other –0.47 (0.39) 0.74

Individual vs. group –0.67 (0.28) 0.02

< 12 weeks vs. 12 weeks 0.12 (0.32) 0.70

> 12 weeks vs. 12 weeks 0.20 (0.44) 0.66

Only studies that used individually delivered psychological interventions were statistically significantly associated with greater effectiveness compared with group-delivered psychological interventions explaining a small proportion of the heterogeneity (adjusted R2 = 12.72%; I2 residual = 81.54%). No multivariable analyses were conducted.

Components network meta-analyses

We fitted four models to assess the impact of different combinations of interventions on reducing trauma. Owing to the instability of models when assessing different trauma scales combined, we conducted all analyses on the CAPS (the most frequently reported trauma scale). Figure 24 shows all of the combinations of intervention components extracted from the studies included. The thickness of the lines for each node are weighted by the number of studies (i.e. the thicker the line, the more studies comparing a particular combination of components with an active control or a waitlist).

Model selection Models 1, 2 and 4 did not fit the data well, reflected by the very high total residual deviance found for each of these models. Model 3 had an acceptable goodness of fit (total residual deviance = 36.33) and the DIC was substantially lower than in other models. Therefore, further analyses were conducted using model 3 (Table 5).

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S+C+IE S+P+C+IE+PH PE+IE S+C+IE+IV IE PE+R+M+C+IE AC AC = active control C = cognitive IE = imaginal exposure S+PE+PH IV = in vivo exposure M = mindfulness WL PE = psychoeducation PH = phase based R = relaxation S+PE+R+C+IE S = support VR = virtual reality exposure PE+R+C+IV+IE WL = waitlist S+PE

PE+R+C+VR+IV S+R+VR+PH PE+R+M+C R+VR S+PE+M

FIGURE 24 Network plot for all combinations of components extracted from the studies included.

TABLE 5 Comparing the goodness of fit for different component network meta-analysis models

Posterior mean Total residual Model deviance DIC deviance τ

Model 1: waitlist, active control, trauma- 25.72 252.99 70.03 0.043 focused CBT, EMDR, mindfulness, DBT, IPT

Model 2: waitlist, placebo, support, 28.60 267.93 70.57 0.042 psychoeducation, relaxation, cognitive restructuring, in vivo exposure, imaginal exposure, virtual reality exposure, mindfulness, phased based

Model 3: waitlist, placebo, support, 30.94 235.45 36.33 0.13 psychoeducation, relaxation, cognitive restructuring, in vivo exposure, imaginal exposure, virtual reality exposure, phased based, support + psychoeducation, psychoeducation + relaxation, psychoeducation + cognitive restructuring, psychoeducation + imaginal exposure, relaxation + mindfulness, relaxation + cognitive restructuring, relaxation + imaginal exposure

Model 4: full interaction model 30.56 264.89 66.09 0.04

Findings from the intervention component network meta-analysis (model 3) The intervention components with evidence of effectiveness and sufficiently precise credible intervals were mindfulness, cognitive restructuring, phase-based approaches, relaxation + imaginal exposure and relaxation + cognitive restructuring (Table 6).

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TABLE 6 Mean difference for outcomes by intervention component

Intervention component Mean difference vs. waitlist (95% CI)

Active control –0.07 (–61.71 to 62.21) Placebo –27.6 (–57.76 to 2.60) Support 16.78 (–13.07 to 47.08) Psychoeducation –0.24 (–30.23 to 29.76) Relaxation 24.32 (–12.12 to 60.56) Mindfulness –32.22 (–53.18 to –10.52) Cognitive restructuring –39.24 (–54.05 to –23.88) Virtual reality exposure –8.6 (–42.08 to 25.84) Imaginal exposure –1.18 (–32.16 to 29.76) Phased based –26.95 (–41.59 to –11.96) In vivo exposure 14.45 (–32.74 to 61.39) Support + psychoeducation 21.3 (–10.29 to 52.64) Psychoeducation + relaxation 32.09 (–6.64 to 70.77) Psychoeducation + cognitive restructuring 10.56 (–8.07 to 29.29) Psychoeducation + imaginal exposure 18.28 (–13.0 to 49.48) Relaxation + mindfulness 28.03 (–17.44 to 73.86) Relaxation + cognitive restructuring –28.29 (–47.56 to –8.79) Relaxation + imaginal exposure –45.34 (–70.86 to –19.52) Mindfulness + cognitive restructuring 28.41 (–16.96 to 74.14) Cognitive restructuring + in vivo exposure 14.31 (–32.8 to 61.41) In vivo exposure + imaginal exposure 15.42 (–18.72 to 49.73)

Acceptability sensitivity analyses

Estimates of attrition in intervention and control groups are likely to be effected by both the acceptability of the intervention and attrition bias. To try to disentangle these factors, we conducted sensitivity analyses including only studies judged to be at a low risk of attrition bias. Table 7 shows the OR of attrition for psychological interventions compared with controls, as presented in Trauma populations earlier, and the OR of attrition for psychological interventions compared with controls for only those trials graded as at a low risk of attrition bias.

Overall, studies with a low risk of attrition bias were associated with reduced odds of dropout from psychological interventions in comparison with controls in all populations combined (14 trials).55,62,64,78,87, 92,98,121,126,131,132,140,144 This trend was seen across trauma experiences (when data were available), although differences between interventions and controls were not always statistically significant. The exception was refugee populations, in which people assigned to psychological interventions were more likely to drop out than those in controls.

Trauma populations that demonstrated a reduced likelihood of dropout in psychological interventions saw a further decrease in the likelihood of dropout when considering only those trials with a low risk of attrition bias. These populations were veterans (three trials),64,78,121 childhood sexual abuse populations (four trials)92,98,131,140 and war-affected populations (two trials),144 but none was statistically significant. In the case of veterans and childhood sexual abuse populations, the reduced odds of dropout were

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TABLE 7 Odds ratios of attrition per population shown across all studies and across only those trials rated as being at a low risk of attrition bias

OR (95% CI)

Population All studies Low risk of attrition bias

All 0.56 (0.40 to 0.80) 0.39 (0.21 to 0.73)

Veterans 0.49 (0.26 to 0.92) 0.44 (0.06 to 3.54)

Childhood sexual abuse 0.24 (0.08 to 0.75) 0.18 (0.03 to 1.00)

Refugee 1.21 (0.69 to 2.12) 2.10 (0.62 to 7.14)

Domestic violence Insufficient data Insufficient data

War affected 0.66 (0.27 to 1.60) 0.11 (0.01 to 1.27) Mixed Insufficient data Insufficient data

statistically significant when considering trials of all risk-of-bias gradings. Therefore, the lack of statistical significance is most likely explained by the reduced statistical power resulting from including only a subset of the data.

In refugee populations, the odds of dropout from psychological interventions were greater than from controls and increased when considering only those trials with a low risk of attrition bias (based on two trials);55,87 however, neither of the pooled ORs was statistically significant.

Adverse events for pharmacological interventions

All of the data relating to adverse events and pharmacological interventions were collated (Table 8). All reporting of further information regarding reasons for withdrawal and adverse events were from veteran populations. Withdrawal owing to adverse events was common across studies, but with relatively small numbers. Practical issues resulting in withdrawal were more frequently reported; there was insufficient detail to infer acceptability from this.

TABLE 8 Pharmacological intervention withdrawals and adverse events as reported

Intervention Authors (year), category population Reasons for withdrawal Adverse events

Antidepressants Becker et al. Bupropion and control overall: allergic Overall: allergic reaction (n = 1) (including (2007),59 reaction (n = 1), transportation difficulties SSRIs) veterans (n = 1), no further interest (n = 1), lost to contact (n = 2) Chung et al. Mirtazapine: lack of efficacy (n = 3), NR (2004),67 personal reasons (n = 3), side effects (n = 1) veterans Sertraline: lack of efficacy (n = 5), personal reasons (n = 1) Davis et al. Nefazodone: adverse effects (n = 5), Nefazodone: drowsiness, dizziness, (2004),73 medication ineffective (n = 2), lost to agitation, gastrointestinal distress, veterans follow-up (n = 4), non-compliance (n = 1) fatigue, orthostatic hypotension, headaches Placebo: adverse effects (n = 1), medication ineffective (n = 2), lost to follow-up (n = 1), Placebo: insomnia, irritability no reason given (n = 2)

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TABLE 8 Pharmacological intervention withdrawals and adverse events as reported (continued)

Intervention Authors (year), category population Reasons for withdrawal Adverse events

Panahi et al. Sertraline: adverse events (n = 2), protocol Sertraline: headache (31%), insomnia (2011),118 violation (n = 1) (31%), nausea (31%), restlessness (25%), veterans diarrhoea (22%), dry mouth (19%), Placebo: adverse event (n = 1), protocol drowsiness (16%), asthenia (16%), violation (n = 2), other (of own accord) decreased appetite (16%), constipation (n = 2) (16%), decreased libido (13%)

Placebo: headache (20%), insomnia (13%), nausea (17%), restlessness (17%), diarrhoea (13%), dry mouth (17%), drowsiness (7%), asthenia (7%), decreased appetite (10%), constipation (10%), decreased libido (7%) Zohar et al. NR Sertraline: nausea (35%), headache (2002),147 (26%), drowsiness (26%), asthenia veterans (17%), increased appetite (13%), dry mouth (13%), decreased appetite (13%)

Placebo: nausea (21%), headache (16%), drowsiness (16%), asthenia (15%), increased appetite (10%), dry mouth (10%), decreased appetite (5%) Antipsychotics Bartzokis Risperidone: adverse effects (n = 11), NR et al. (2005),58 unrelated medical condition (n = 1), alcohol veterans abuse (n = 1), discontinuing medication (n = 1), lost to follow-up (n = 5)

Placebo: adverse effects (n = 6), alcohol abuse (n = 1), lost to follow-up (n = 3) Monnelly et al. Risperidone: episode of urinary retention Risperidone: mild adverse event (n = 4) (2003),110 (n = 1) veterans Placebo: mild adverse event (n = 2), moderate adverse event (n = 1) Stein et al. Olanzapine: (early protocol terminations) Olanzapine: weight gain change of (2002),135 somnolence (n = 2), unspecified (n = 1) +13.2 lb (SD 5.9 lb) veterans Placebo: lack of efficacy (n = 1) Placebo: –3 lb (SD 6.5 lb) Anticonvulsants Davis et al. Divalproex: adverse events (n = 3), serious NR (2008),72 but unrelated adverse event (n = 1), failure veterans to return (n = 2), lost to follow-up (n = 4)

Placebo: adverse event (n = 1), lack of efficacy (n = 1), lost to follow-up (n = 4) Lindley et al. Topiramate: adverse events (n = 6), Topiramate: reported in 17 patients (2007),104 clinician withdrew because of adverse veterans event (n = 2), significant worsening of Placebo: reported in 16 patients symptoms (n = 1), left residential treatment (n = 1), discharged by clinical staff owing to behaviour (n = 1)

Placebo: adverse event (n = 1), clinician withdrew because of adverse event (n = 1), left residential treatment (n = 12), discharged by clinical staff owing to behaviour (n = 1) continued

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TABLE 8 Pharmacological intervention withdrawals and adverse events as reported (continued)

Intervention Authors (year), category population Reasons for withdrawal Adverse events

Prazosin Raskind et al. Prazosin: adverse event (n = 1), opted for Prazosin: hospitalisation for suicidal (2013),123 open-label prazosin (n = 1), too busy (n = 1), ideation (n = 1), suicide attempt with veterans lost contact (n = 1) non-lethal overdose of oxycodone/ acetaminophen (n = 1); syncope (3%), Placebo: opted for open-label prazosin (n = 1), light-headedness (25%), nasal too busy (n = 2), lost contact (n = 3) congestion (22%), palpitations (6%), drowsiness (3%), muscle weakness (3%), headaches (3%)

Placebo: light-headedness (20%), nasal congestion (11%), lack of energy (3%), palpitations (3%), drowsiness (9%), depression (6%), headaches (23%) SD, standard deviation.

Non-randomised studies of clinical effectiveness

Post-traumatic stress disorder symptoms Six of the nine non-randomised studies reported PTSD outcomes.148–150,152,155,156 Effect sizes were calculated for four of these studies (representing five interventions), as they used inactive control comparators (Table 9).149,152,155,156

TABLE 9 Non-randomised trial intervention characteristics and effects on PTSD outcomes

Post-treatment Authors effect, SMD (year) Population Intervention (category) Control Scale (95% CI) n

Kruse et al. Refugees Trauma-focused Treatment as HTQ –2.54 64 (2009)149 psychotherapy (non- usual (–3.21 to –1.88) trauma-focused CBT) Morgan and Childhood Group therapy No DSM-III subscales –0.18 80 Cummings sexual (multicomponent intervention (–0.62 to 0.26) (1999)152 abuse trauma-focused intervention) Salo et al. War Individual therapy Waitlist HTQ: 0.00 95 (2008)155 affected (trauma-focused CBT) re-experiencing (–0.50 to 0.50) HTQ: avoidance –1.22 95 (–1.75 to –0.69) HTQ: –1.50 95 hyperarousal (–2.04 to –0.95) Group therapy HTQ: 0.32 96 (multicomponent non- re-experiencing (–0.18 to 0.81) trauma-focused intervention) HTQ: avoidance 2.66 96 (2.04 to 3.28) HTQ: 0.74 96 hyperarousal (0.24 to 1.25) Saxe and Childhood ‘Victim to survivor’ No IES intrusion –0.09 63 Johnson sexual group therapy intervention subscale (–0.58 to 0.41) (1999)156 abuse (trauma-focused CBT) IES avoidance –1.01 63 subscale (–1.53 to –0.48) HTQ, Harvard Trauma Questionnaire; IES, Impact of Events Scale.

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Trauma-focused interventions Two studies in trauma-focused CBT saw a significant reduction in PTSD avoidance symptoms.155,156 One study investigated ‘victim to survivor’ group therapy in a childhood sexual abuse population156 (SMD –1.01, 95% CI –1.53 to –0.48; n = 63) and the other investigated individual therapy in a war-affected population155 (SMD –1.22, 95% CI –1.75 to –0.69; n = 95). Individual therapy in a war-affected population also showed a large and significant effect in reducing PTSD hyperarousal symptoms (SMD –1.50, 95% CI –2.04 to –0.95; n = 95), but was equivalent to the waitlist at reducing PTSD re-experiencing symptoms.155

One study examined a multicomponent trauma-focused intervention delivered in a group format to a childhood sexual abuse population.152 A small reduction in PTSD symptoms was found, but this was not significant.

Non-trauma-focused interventions Non-trauma-focused CBT was investigated in one study in a refugee population and showed a large and significant effect favouring group intervention for reducing PTSD symptoms (SMD –2.54, 95% CI –3.21 to –1.88; n = 64).149

Multicomponent non-trauma-focused therapy was investigated in just one study of war-affected individuals155 and showed significant effects favouring controls for PTSD hyperarousal (SMD 0.74, 95% CI 0.24 to 1.25; n = 96) and avoidance symptoms (SMD 2.66, 95% CI 2.04 to 3.28; n = 96). A small, insignificant effect on PTSD re-experiencing symptoms also favoured the control group.

Head-to-head comparisons Two148,150 of the non-randomised studies reporting PTSD outcomes were head-to-head comparisons conducted in veteran populations.

One comparison of trauma-focused CBT versus psychodynamic psychotherapy reported a significant reduction in PTSD symptoms (clinician- and patient-rated), with no significant difference between interventions.150

A comparison of mindfulness-based cognitive therapy with a mixed comparator of active interventions reported a significant reduction in PTSD symptoms for those undergoing mindfulness-based cognitive therapy, but not the mixed comparator.148

Depression Five non-randomised studies150–153,156 reported depression outcomes. Of these, four studies150–152,156 used inactive comparators. Effect sizes were calculated for three studies (constituting four interventions); outcome reporting prohibited this for one study,153 so it is described as published (Table 10).

Trauma-focused interventions All studies for which SMDs were calculated were trauma-focused interventions, delivered in a group format, to childhood sexual abuse populations.

Two studies reported depression outcomes for three trauma-focused CBT interventions. In one study,151 a short-term therapy demonstrated an insignificant and small effect of increasing depression (compared with control); the same study found an insignificant and small effect of group therapy reducing depression. Another study156 of trauma-focused CBT in group therapy showed a large and significant effect for decreasing depression symptoms on two scales: the Beck Depression Inventory (–1.53, 95% CI –2.09 to –0.97; n = 63) and the Center for Epidemiologic Studies Depression Scale (–1.19, 95% CI –1.73 to –0.65; n = 63).

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TABLE 10 Non-randomised trial intervention characteristics and effects on depression outcomes

Post-treatment effect, SMD Authors (year) Population Intervention Control Scale (95% CI) n

Lundqvist et al. Childhood Group therapy Waitlist SCL-90: –0.31 52 (2006)151 sexual abuse (trauma-focused CBT) depression (–1.00 to 0.38) Short-term therapy SCL-90: 0.11 28 (trauma-focused CBT) depression (–0.66 to 0.89)

Morgan and Childhood Group therapy No BDI –0.43 80 Cummings sexual abuse (multicomponent intervention (–0.88 to 0.01) (1999)152 trauma-focused intervention)

Saxe and Childhood ‘Victim to survivor’ Waitlist BDI –1.53 63 Johnson sexual abuse group therapy (–2.09 to –0.97) (1999)156 (trauma-focused CBT) CES-D –1.19 63 (–1.73 to –0.65) BDI, Beck Depression Inventory; CES-D, Center for Epidemiologic Studies Depression Scale; SCL-90, Symptom Checklist 90.

Based on one study,152 multicomponent trauma-focused group therapy was associated with a moderate treatment effect in favour of a reduction of depression and this was of borderline significance (SMD –0.43, 95% CI –0.88 to 0.01; n = 80).

In one study,153 a SMD was not calculated owing to outcome reporting. This compared both EMDR and trauma-focused CBT with a control in a war-affected population. The reported results stated that both interventions significantly reduced depression symptoms with no significant difference between EMDR and CBT, suggesting effectiveness.

Head-to-head comparisons One study150 reported a direct comparison of trauma-focused CBT with psychodynamic therapy in veterans. A significant reduction in depression symptoms was reported following treatment, with equivalent effectiveness between therapies.

Anxiety One151 of the nine non-randomised studies included in this review reported anxiety outcomes for two interventions. The findings are presented in Table 11.

TABLE 11 Non-randomised trial intervention characteristics and effects on anxiety outcomes

Post-treatment effect, SMD Authors (year) Population Intervention Control Scale (95% CI) n

Lundqvist et al. Childhood Group therapy Waitlist SCL-90 anxiety –0.16 52 (2006)151 sexual abuse (trauma-focused CBT) (–0.85 to 0.53) Short-term therapy SCL-90 anxiety 0.16 28 (trauma-focused CBT) (–0.62 to 0.93) SCL-90, Symptom Checklist 90.

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Trauma-focused interventions Two trauma-focused CBT interventions were both compared with control in a childhood sexual abuse population.151 Group therapy was associated with a small reduction in anxiety symptoms, while short-term therapy was associated with a small increase compared with control. Neither finding was significant.

Quality of life None of the non-randomised studies included reported quality-of-life outcomes.

Sleep quality None of the non-randomised studies included reported sleep quality outcomes.

Attrition Six148–151,155,156 of the non-randomised trials included reported attrition data for eight comparisons. All were compared with a control group, with the exception of one active control trial148 and one head-to-head comparison.150 ORs were calculated for all controlled trials and are presented in Table 12.

Only one trial,155 investigating two interventions, reached significance. There was a reduced likelihood of dropout in both the trauma-focused CBT and the multicomponent non-trauma-focused intervention compared with control in a war-affected population.

Three trauma-focused CBT interventions in a childhood sexual abuse population had reduced odds of attrition among those receiving the intervention, but large CIs resulting in uncertain estimates.151,156 A non-trauma-focused CBT intervention in a refugee population showed increased odds of dropout among those receiving the intervention compared with those in the control; this finding also had wide CIs and was not significant.149

TABLE 12 Odds ratios of attrition for each trial reporting data

Trauma OR of attrition Authors (year) population Intervention category vs. control (95% CI) n

Kruse et al. (2009)149 Refugees Non-trauma-focused CBT 2.06 (0.19 to 23.83) 70

Lundqvist et al. (2006)151 Childhood (Group) trauma-focused CBT 0.58 (0.03 to 12.08) 55 sexual abuse (Short-term) trauma-focused CBT 0.20 (0.01 to 4.01) 32

Salo et al. (2008)155 War affected Trauma-focused CBT 0.02 (0.00 to 0.36) 106

Multicomponent non-trauma-focused 0.00 (0.00 to 0.08) 106 intervention

Saxe and Johnson (1999)156 Childhood Trauma-focused CBT 0.51 (0.16 to 1.61) 108 sexual abuse

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Chapter 5 Results of the qualitative acceptability review

Studies included

In total, 1609 titles and abstracts were screened and 1560 were excluded. In addition, 49 full-text papers were screened and 41 were excluded, with the reasons summarised in Figure 25. We included nine papers, constituting eight unique studies, that were found to use qualitative methods or a mixed-methods approach with a strong qualitative component. Qualitative components included data collection using interviews (unstructured or semistructured) and focus groups, and the data were analysed following a qualitative methodology, with methods such as thematic analysis, ethnography or a phenomenological approach.

Of the studies selected for inclusion in the qualitative review, the majority were from North America (n = 7); two studies were performed in Canada but most of the research was performed in the USA (n = 5). The other studies were performed in Bangladesh (n = 1) and the UK (n = 1).

In terms of the types of trauma that participants were exposed to, four studies involved participants exposed to intimate partner violence,161–164 of which two are linked.163,164 Two studies involved veterans,165,166 two studies involves participants exposed to childhood sexual abuse167,168 and one study involved asylum seekers.169

The intervention classifications include group mindfulness-based stress reduction (MBSR; n = 3163–165), motivational interviewing (n = 1162), prolonged exposure (n = 1166), mental health counselling (n = 1161), group healing or group treatments (n = 2167,168) and trauma-focused CBT (n = 2166,169), which, in one case, was a combined treatment with prolonged exposure (n = 1166). Table 13 provides details of all of the studies included.

Records identified through database Additional records identified searching through other sources (qualitative n = 4289) (n = 35)

Records after duplicates removed (qualitative n = 1609)

Records screened Records excluded (n = 1609) (n = 1560)

Full-text articles assessed Full-text articles excluded, for eligibility with reasons (n = 49) (n = 41) • Population, n = 8 • Intervention, n = 13 • Outcome(s), n = 8 Studies included in • Study design, n = 10 qualitative synthesis • Language, n = 1 (n = 8) • Protocol, n = 1

FIGURE 25 The PRISMA diagram of the flow of records through the review process.

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TABLE 13 Risk-of-bias assessment of the qualitative studies included using the CASP tool www.journalslibrary.nihr.ac.uk

Authors (year)

Hughes and Hundt et al. Martinez et al. aBermudez aDutton et al. Rasmussen Naved et al. Palmer et al. Parker et al. Vincent et al. Research question (2017)166 (2015)165 et al. (2013)163 (2013)164 (2010)162 (2009)161 (2007)167 (2007)168 (2013)169

1. Was there a clear statement of the aims of YY Y Y YYY Y Y the research?

2. Was a qualitative methodology appropriate? Y Y Y Y Y Y Y Y Y 3. Was the research design appropriate to YY Y Y YCY Y Y address the aims of the research?

4. Was the recruitment strategy appropriate to YY Y Y NNC Y Y the aims of the research?

5. Were the data collected in a way that YY Y Y YYY Y Y addressed the research issue?

6. Has the relationship between researcher and CC C Y YYY Y C participants been adequately considered? 7. Have ethical issues been taken into YY Y C YYC Y Y consideration?

8. Was the data analysis sufficiently rigorous? Y Y Y Y C C Y Y C

9. Is there a clear statement of findings? Y Y Y Y Y Y Y Y Y 10. How valuable is the research? Score 8.5 Score 8.5 Score 8.5 Score 8.5 Score 7.5 Score 7.5 Score 8.0 Score 9.0 Score 8.0 C, cannot say; N, no; Y, yes. a Linked studies. DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Quality of the studies included: Critical Appraisal Skills Programme assessment

Methodological limitations were assessed with the CASP qualitative checklist to facilitate the assessment of both study design and implementation, as described in the GRADE-CERQual recommendations.51 The studies included were assessed for methodological limitations using a modified version of the CASP in which the individual elements for the quality assessment (see Table 13 for the CASP checklist) were used in conjunction with a scoring system. A full score of 9.0 for the CASP assessment allowed a CERQual score of ‘no concerns’ as regards the methodological limitations of the studies included, as well as the relevance and coherence of data with regard to integration across the review themes.

The majority of the studies were allocated less than the maximum score of 9.0, as information was not clearly apparent in the methods of the paper. This contributed to a CERQual assessment of ‘minimal concerns’ for the integration of research findings for this review. When no score was given, the CERQual score was registered as ‘significant concerns’; the only instance of this was attributed to selection bias for the participant selection, as many studies experienced difficulties in recruiting participants and, as such, studies enrolled a small number of participants or a convenience sample.

Table 13 presents the findings of the CASP assessment and the tables in Appendix 9 provides additional information on the study details and their methodological assessments.

Narrative synthesis

All of the studies included offered in-depth accounts of service user experiences of psychological interventions either delivered in health- or social-care or settings or by voluntary agencies. Population subgroups included veterans, people with a history of childhood sexual abuse, people with a history of domestic violence and asylum seekers. Using acceptability and feasibility as organising meta-themes, we identified three core subthemes across these populations:

1. therapeutic context 2. skills strengthening 3. self-efficacy and reward.

Therapeutic context

Group-based therapies This theme captured data that spoke to service users’ perspectives on the merits of engaging in therapeutic interventions in groups and how feasibly these group-based approaches aligned with the therapeutic orientation and goals of the intervention. For non-trauma-focused interventions such as mindfulness, there was an understanding that delivering interventions in groups was potentially a safe and advantageous way to connect with others who have had similar traumatic experiences without fear of re-traumatisation. This was especially true of women with a history of domestic violence: ‘Having had common traumas made it easy to relate to other participants. I was able to revisit traumatic situations without judgement.’163

However, this perspective was not universally shared, with a contrary finding among veterans, whose overall perception of mindfulness was positive but was layered with misgivings about taking part in groups. For some participants, groups were less acceptable because their PTSD symptom profile made them feel ‘uncomfortable in groups’, with the risk that interactions with other group members were counterproductive to the therapeutic goals of achieving serenity and non-judgemental self-awareness: ‘I had such issues with certain people and one of them couldn’t sit still. I would turn around and he kept staring at me. I was not comfortable.’165

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Women with a history of childhood sexual abuse also voiced similar concerns about the negative impact of taking part in groups as part of more trauma-focused interventions:

[I] found it hard to break through the barriers that I’d already set up . . . a lot of trust issues with the group . . . I was still just breaking the ice . . . about my sexuality . . . I saved it right up to the very last day. Palmer et al.167

The idea that group approaches were not always an acceptable platform to engage people with complex trauma histories was also linked to concerns that group-based activities that focused on trauma experiences risked re-traumatising participants: ‘I would come out of [the process groups] exhausted, even if I didn’t say anything . . . just listening to other people’s stories was very draining.’167

Scheduling and setting Another key feature of the therapeutic context that underpinned perceptions about the acceptability and feasibility of interventions was that scheduling and the setting of treatments were important determinants of participants’ satisfaction and engagement with therapy. Veterans that were signed up to mindfulness noted that scheduling could be a practical barrier to attendance.165 More critically, among women with a history of domestic violence, there were widely voiced concerns that waiting times and the length of treatment sessions for counselling could increase the risk of further abuse at home if they returned late.161 This highlighted the importance of providing treatment in a safe and caring environment that offered participants sanctuary and the security to engage in treatment, as reported by women with a history of domestic violence who were given classes in motivational interviewing at a shelter: ‘You deserve the caring, and you deserve to be treated well.’162

The need for additional wraparound care to help facilitate engagement with treatment was especially salient among women exposed to domestic violence who had children and felt frustrated that their family needs were not often met:

I was takto [irritated/annoyed] . . . I was annoyed that I left my child in the corridor. They took me to another room . . . The child was crying. Naved et al.161

Skills strengthening Participants’ ratings about the acceptability of interventions were also associated with the extent to which they perceived interventions as strengthening their personal and interpersonal skills. This was especially true among participants who had experience of non-trauma-focused interventions such as mindfulness and motivational interviewing. MBSR was particularly earmarked by women with a history of domestic violence as conferring opportunities to use newly acquired skills in self-compassion and self-awareness to regulate their emotions and manage their stress more effectively, because they ‘felt they had learned how to quiet their minds’.163,164

Beyond the recognition that non-trauma-focused interventions can bring about positive steps towards self-actualisation through personal development, there were also signals that treatment acceptability hinged on the broader impact on participants’ interpersonal skills. Women with a history of domestic violence voiced how taking part in motivational interviewing had enabled them to more effectively engage in other treatment services. In addition, for some participants, these interpersonal benefits spilled over into the domestic sphere, positively affecting the way that they interacted with partners and underpinning a newly derived confidence to engage in family life:

My confidence has gone up a great deal . . . Even though I came in self-confident in some areas of my life, I think that when it comes to specifically how I relate with my husband in that area, it’s boosted it up completely. I think that I’m capable. Hughes and Rasmussen162

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Self-efficacy and reward Related to the notion that interventions were more acceptable if they led to strengthening of personal and interpersonal skills was the finding that participants tended to favour interventions that made intuitive sense, rewarded persistence and were demonstrably effective. In this sense, the more self-efficacious participants felt about fulfilling the requirement of treatment sessions, the more likely they were to persist with treatment; this bi-directional relationship was also reinforced by visible signs of recovery. Dropout and attrition were more common among participants who engaged in interventions that they struggled to identify with and master, with mindfulness being singled out by veterans, among the non-trauma-focused interventions, as challenging:

I just didn’t get it. I was so stupid when I first went to it the last time. I didn’t even realise what I was supposed to be doing . . . I felt ignorant and embarrassed so that’s why I quit. Martinez et al.165

By contrast, although trauma-focused interventions such as prolonged exposure and cognitive processing therapy could initially lead to a worsening of symptoms, veteran participants recognised that it was likely to be ultimately effective and ‘worth it’.166

In part, participants’ willingness to stay the course in trauma-focused treatment stemmed from a ‘commitment to finish’, born from a realisation that their time had come to ‘turn things around’, to paraphrase a male veteran, a theme that was voiced by other veterans engaged in cognitive processing therapy:

Yes, I did [consider dropping out] because I was avoiding having to write out my traumatic experience but I knew I had to do it . . . I can’t keep burying my head in the sand. Hundt et al.166

For others, participation in trauma-focused work was made feasible only through engagement with a supportive therapist. In this context, a positive therapeutic alliance conferred the means to stay focused on treatment goals:

I loved [therapist name]; she was great and she was patient and she helped keep me focused . . . that made it a little bit easier to show up. Hundt et al.166

The tone of participants’ ratings about trauma-focused interventions differed depending on their circumstances, with asylum seekers, who feared deportation, more likely push themselves to take up treatment on the grounds that it will be effective:

I used to force myself to do it just because I feel that it’s going to help me. Vincent et al.169

Despite ongoing fears of repatriation and a sense of creeping fatalism among asylum seekers, there were participants whose ability to see signs of progress encouraged them to continue to push themselves to take up therapy:

. . . I started maybe feeling a bit of difference. That’s when I used to force myself ‘You have to go. No, be strong, go and they are helping you’, so I end up going. Vincent et al.169

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Summary In summary, the acceptability of interventions was associated with how congruent they were with participants’ therapeutic needs and social contexts, and the means by which the interventions were able to provide participants with opportunities to engage in personal and interpersonal improvement and confer demonstrable improvements. The feasibility of interventions hinged on more instrumental features, such as the scheduling and timing of treatment sessions.

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Chapter 6 Patient and public involvement and the research prioritisation exercise

lthough the overarching focus and framework of the current review was prespecified by the Acommissioned brief, we recognise that patient and public involvement (PPI) in systematic reviews is a critical means to ensure that the research process and products are more accessible, relevant and meaningfully used through active involvement of service users (known as ‘experts by experience’) and key stakeholders.170 However, there is a broad range of conceptual models of service user involvement in systematic reviews, from one-off consultation to ongoing collaboration, and early engagement with potential contributors at a conceptual level is likely to shape the content and style of user involvement.171

Our strategy was informed by an understanding that knowledge mobilisation is a dynamic and interactive process that is reliant on forming equitable transactional relationships with patients, the public and stakeholders.172 Our user engagement strategy was informed by an understanding that experts by experience can bring critical insights and perspectives that can add value to contextualising the findings of our review and contribute to enhancing the reach of dissemination activities, especially in relation to setting future research priorities.

Aims

Our PPI strategy had three broad aims:

1. to consult with experts by experience about the focus and design of the review 2. to contribute to identifying research priorities 3. to contribute to dissemination of the findings of the review, including the research priorities.

Aim 1: consultation on the overall aims and design of the review

Methods To identify people with a history of complex traumatic events, we approached The Retreat hospital, York, or service user groups that were known to us through our clinical experience of working in the field. We have not named the groups involved in this consultation exercise to protect the identity of the service users.

Participants Ten people (six women and four men) who had used inpatient and secondary care mental health services, all with a history of complex trauma, took part in the focus groups. Trauma histories included childhood sexual abuse, sexual assault as adults, self-harm and domestic violence. Some had experienced homelessness and had been offenders; comorbidities and symptom profiles included drug and alcohol addictions, suicidality and dissociated identities. All of the service users identified were all currently using or had recently used NHS mental health services and/or third-sector mental health services. None of the subjects was approached within an NHS setting or directly through NHS services.

Research governance approval to contact and identify eligible service users who had been patients at The Retreat was granted on 31 July 2017 by Dr Mark McFetridge, Chairperson of the Clinical Governance Group at The Retreat, York.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 65 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. PATIENT AND PUBLIC INVOLVEMENT AND THE RESEARCH PRIORITISATION EXERCISE

Format and timing of focus groups Interviewing people who are currently using mental health services or who are still acutely affected by their symptoms is difficult owing to the sometimes chaotic nature of engagement with services, as well as the sensitivity and care needed to avoid causing harm to these subjects. An expert by experience (the Involvement Lead at The Retreat) and a specialist trauma psychotherapist (IS) carried out the interviews so that the risk of re-traumatisation was minimised. Following the interviews, all of the subjects had access to mental health nursing staff or support workers with whom they had an existing relationship.

Four focus groups were conducted between May and July 2018. Where possible, focus groups were carried out at times when the service users were already planning to meet so that the researchers could align the focus groups with an existing structured timetable, thereby minimising disturbance to the service users’ schedule.

Topic guide A structured topic guide was used to ensure that each focus group addressed similar issues pertinent to the review process. Participants were given copies of lay summaries of the project protocol that specified and explained the criteria for the population, interventions, comparisons and outcomes used to determine inclusion within and exclusion from the eligible studies. In addition, participants were given lay summaries of the descriptive results of the effectiveness review that characterised the number of studies included, the types of populations included and the characteristics of the interventions included. The following questions and prompts were used to elicit responses about the aims and focus of the review, with a view to generating feedback about the scope of the current review and future research priorities:

1. Which populations should be included in the study?

l Do you feel this is an accurate representation of populations with a history of trauma? l What other groups do you think should be included? l Do you think this is the right balance of studies on each population?

2. What types of therapies should be included in the review?

l Is this an accurate representation of the therapies available for people with a history of trauma? l Do you know of any therapies for trauma that have not been included here? l Do you think this is a good balance of therapies included in the systematic review? l Are there any additional psychological interventions that should be included? l Do you think any of the therapies included to date require further research?

3. Which medicines should be included in the review?

l What other types of medicine are prescribed to individuals with complex trauma? l What do you think about the balance of studies on each type of medication included in the systematic review?

Results

Theme 1: under- or over-representation of populations of interest There were a number of responses that clustered around discussions of certain population groups exposed to complex trauma being either under- or over-represented in the review: ‘It’s important to include all populations to get the scale of it’.

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In general, participants suggested that female populations were seen as under-represented within population groups that might typically be associated with males, such as veterans: ‘...it’s strange; it’s [the review] so male dominated because most domestic abuse happens to women’.

Respondents suggested that groups such as people in drug and alcohol services and those that foster children should be included. In addition, participants who had experienced treatment in inpatient settings suggested that studies that evaluated treatments among inpatients were under-represented and pointed to the complexity of their symptoms as indicative of the need for a broader formulation of what complex trauma is: ‘. . . people associate trauma with war, but PTSD is not the same as complex trauma’ and ‘. . . it can be a fine line between stress and trauma’.

Theme 2: mind and body separation Participants highlighted that the review was possibly focused on a narrow range of symptoms associated with mental health alone, with too little focus on understanding the impact of complex trauma on physical functioning: ‘why does it just include psychological therapies? There is a mind–body separation here’.

This awareness of a mind–body separation was reflected by participants acknowledging that the therapies included in the review were prescriptive and manualised psychological interventions, with a focus on mental health symptom management rather than more humanistic and integrative therapies, such as transactional analysis and Gestalt, which look to overcome such mind–body dualism: ‘...are trauma-focused CBT and exposure therapies really integrative therapies? . . . humanistic therapies should be added as a category of their own’.

Similarly, participants noted that there is also scope to learn more about the effectiveness of therapies that address the somatic impact of complex trauma, such as alternative and complimentary therapies such as yoga and kinesiology: ‘. . . lots of trauma relates to the body’.

There was also a sense that future research should address the effectiveness of therapies for people who had limited access to existing evidence-based treatments owing to learning difficulties and language barriers.

Theme 3: further work on pharmacological therapies Fewer studies about pharmacological interventions have been included in the current review and service users’ own experiences were predominantly drawn from their experience of psychological interventions. However, there was an awareness that, in the current review, many of the studies that evaluated the effectiveness of medications were focused on medications used for severe and enduring mental health problems (such as personality disorder rather than PTSD) and it was not clear if there was sufficient understanding about the role of a broader range of medications in managing symptoms across the complex trauma experience.

Aims 2 and 3: setting research priorities and disseminating findings

Process A stakeholder research prioritisation day was held on 9 July 2018 to present preliminary quantitative and qualitative findings. The goal was to identify research priorities and co-produce with stakeholders a ranked list of future research questions. Attendees were practitioners with interest and experience in complex trauma, voluntary and third-sector providers of services to people affected by complex trauma, and experts by experience.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 67 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. PATIENT AND PUBLIC INVOLVEMENT AND THE RESEARCH PRIORITISATION EXERCISE

The team from Beyond The Room (http://beyondtheroom.net/) facilitated online voting and online public engagement via social media. A Twitter account was set up (@UoY_INCiTE) and a hashtag for the project (#INCiTEstudy) was also active throughout the day, alongside the Beyond The Room social media account, to disseminate information being shared at the event and to invite non-participants on the day to engage in the voting.

Future research priorities were co-produced in a workshop format, following the presentation of results. Three break-out groups discussed their perspectives on the range of evidence presented and identified important unanswered questions. The role of the review team was to help facilitate development of research questions and offer guidance about appropriate methodologies that could be feasibly used to address the questions identified within the groups.

Research priorities were then collated online using MentiMeter (www.mentimeter.com), an online voting platform provided by the Beyond The Room team. This platform enabled online voting among participants in the room but also facilitated wider engagement with voting on research priorities from those not present but following the discussions on the INCiTE Twitter account. Each participant was awarded 100 points to allocate to the long-list of research questions.

Participants were encouraged to promote further engagement in the voting exercise by advertising the voting link with interested people in their networks. Voting was open for 1 week following the event and closed on 16 July 2018.

Results On the day, there were 16 attendees (plus the review team) who were from:

l The Retreat, York l Tees, Esk and Wear Valleys NHS Foundation Trust, Darlington l Combat Stress, Surrey l Home-Start, York l IDAS (Independent Domestic Abuse Services), York l University of Manchester, Manchester l University of York, York.

The research priorities developed during the prioritisation event are listed in Table 14. A total of 68 people took part in the online vote. The proportional share of points awarded to each priority is also shown.

A majority of the points were awarded to just 4 of the 13 research priorities, accumulating over 10% each. A definitive trial of the effectiveness of interventions with a long-term follow-up and a peer researcher exercise to understand the lived experience of people with experience of complex trauma were the two most favoured priorities, with both having a similar percentage of vote share.

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TABLE 14 Research priorities developed from research prioritisation exercise attendees and the share of the online vote

Research priority Vote share (%)

Conduct a definitive trial of the effectiveness of interventions in complex trauma, with long-term 15.91 follow-up (e.g. 24 months)

Understand the lived experience of people with experience of complex traumatic events: a peer 14.80 researcher exercise

Conduct a qualitative study exploring the patient perspective on key outcomes, preferred therapies, 12.48 acceptability and delivery format of interventions (e.g. group or individual)

Develop holistic and biopsychosocial assessment, prioritising a mind–body approach 10.46

Understand what the core outcomes for patients, families and health-care providers are 7.55 (e.g. appropriate outcome domains and measures, including adverse outcomes)

Understand how best you engage populations with experience of complex traumatic events 6.43

Understand what the key outcomes that should be included in trials are 6.28

What are the key components of an effective multicomponent intervention? (e.g. support in 5.83 engaging in work, debt management)

Test the feasibility of social prescribing for wraparound care for people with complex traumatic 5.68 experiences

Understand what the core components and domains of interventions and integrated approaches are 4.71 (e.g. individual vs. group plus individual therapy)

Understand how we can define good practice. Use a Delphi survey to capture perspectives on 3.74 positive recovery stories and barriers to and facilitators of retaining patients in care

Understand how we best taper off psychological interventions 3.14

Understand what the optimal duration of treatment is 2.99

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 69 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Chapter 7 Discussion

Summary of results across all populations with complex trauma for post-traumatic stress disorder

We included 104 studies in the effectiveness review and reported 37 comparisons using meta-analysis across 79 RCTs. There were a total of nine non-RCTs that included five comparisons for PTSD, four comparisons for depression and two comparisons for anxiety. The number of non-RCTs included in the review was much lower than anticipated and we identified a greater volume of trial evidence than was anticipated. This may have been because we adopted a strategy that favoured including studies based on trauma exposure rather than diagnostic criteria and thereby we were able to identify a much broader range of studies pertaining to complex trauma. However, the merit of including data from non-RCTs was diminished by the fact that these studies rarely reported the same intervention types or outcomes, making meta-analyses less possible. Overall, the quality of the available evidence was unclear, with the lowest risk observed in domains related to detection bias, random sequence generation and other risks of bias and the highest risk of bias observed in performance bias and attrition domains. The majority of studies were at high risk of performance bias, partially explained by the predominance of psychological interventions included in the review and the challenges of blinding their delivery. When pooled across all populations with complex trauma, psychological interventions were proven to be effective at reducing PTSD symptoms when compared with control post treatment. There was less evidence that this finding held when treatment effects were measured up to 6 months post treatment, with only trauma-focused CBT and single-component trauma-focused interventions showing positive effects over the longer term. There was no significant difference in the effectiveness of psychological interventions for PTSD symptoms when compared with active controls.

The bulk of the evidence across all populations for reducing PTSD symptoms favoured trauma-focused CBT when compared with control post treatment and at follow-up after up to 6 months. There was no evidence of the effectiveness of trauma-focused CBT versus active controls and this is a weakness of the set of trials analysed. IPT and EMDR were also superior to control post treatment but there was less evidence that mindfulness improves PTSD symptoms in the presence of complex trauma. Non-trauma-focused CBT was not effective at any time point. These findings were reflected in the meta-analysis that showed that single-component and trauma-focused interventions were more effective than control post treatment and at follow-up and outperformed multicomponent and trauma-focused interventions post treatment. Collectively, single-component non-trauma-focused interventions that included approaches beyond CBT were effective post treatment, but these approaches were the least best option for managing PTSD symptoms across all populations.

Few studies addressed the symptom cluster associated with CPTSD and, of those that did, the majority focused on emotional dysregulation. We found no evidence that either trauma- or non-trauma-focused psychological interventions were superior to control in improving emotional dysregulation or interpersonal problems post treatment. By contrast, psychological interventions post treatment were associated with large and positive effect sizes for improving negative self-concept, with multicomponent trauma-focused interventions outperforming all other approaches. There was some evidence that phase-based approaches that allow for stabilisation work to be done before exposure to trauma-focused interventions are the most promising candidate intervention for managing emotional dysregulation and interpersonal problems, although the superiority of these approaches over control was not statistically significant.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 71 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. DISCUSSION

Summary of results for psychological interventions across populations for depression and anxiety Collectively, psychological interventions were shown to be superior to control, but not to active control, both post treatment and at follow-up for managing associated symptoms of depression in all populations with complex trauma. There was strong evidence that trauma-focused CBT post treatment was a highly effective treatment for managing depression in people exposed to complex trauma, but there was less evidence that these effects are present at 6 months’ follow-up. IPT and EMDR were similarly associated with large treatment effects for reducing depression when compared with control, but not active control, post treatment, but evidence in favour of these approaches was thin. Mindfulness was also superior to control post treatment; it was also effective at 6 months’ follow-up, but evidence for this finding is inconclusive. While single-component non-trauma-focused interventions that included mindfulness-based approaches were effective in reducing depression symptoms post treatment, the most consistent and largest effects for depression post treatment and at 6 months’ follow-up were observed in trials that tested single-component and trauma-focused interventions.

A similar set of results were returned in the meta-analyses that assessed the effectiveness of psychological interventions across all populations for reducing associated symptoms of anxiety. All analyses for this outcome were conducted post treatment. Trauma-focused CBT emerged as a leading candidate intervention for reducing anxiety symptoms in the presence of any type of complex trauma, with interventions associated with medium to large effect sizes. The largest effects were observed in trials that compared EMDR with control, albeit this finding was based on relatively few trials. In summary, trauma-focused approaches, when delivered as either a single-component or a multicomponent intervention, were superior to control for anxiety symptoms when effects were pooled across all populations.

We found no evidence that psychological interventions in general, and trauma-focused CBT in particular, were effective in improving quality of life across all populations. There was a modest amount of evidence in favour of trauma-focused CBT for managing sleep problems when results were pooled across all populations.

Summary of population subgroup analyses

Veterans Among veterans, psychological trauma-focused CBT and EMDR emerged as the most effective individual psychological interventions for reducing PTSD symptoms post treatment. There was little evidence to show that mindfulness was an effective therapeutic strategy in this group and, overall, single-component non-trauma-focused interventions were not superior to control either post treatment or at follow-up. Multicomponent and trauma-focused interventions were the most effective approaches among veterans for managing PTSD symptoms.

Psychological interventions, in general, are effective for managing depression in veterans exposed to complex trauma. When effects were pooled across all interventions, the SMD post treatment represented a medium and positive effect in favour of reducing depression, but this effect was about half the size observed in the analysis across any type of trauma exposure. The most effective interventions for depression among veterans were trauma-focused CBT and EMDR, and these positive and large effects held when trauma-focused interventions were delivered as either a single-component or a multicomponent approach. Limited evidence from non-RCTs suggested that trauma-focused CBT and psychodynamic therapy had equivalent positive effects for depression in veterans. The least effective but still positive approaches for depression in veterans were mindfulness and single-component non-trauma-focused interventions, which yielded moderate treatment effects.

Similarly, psychological interventions were, on the whole, effective at reducing associated anxiety symptoms in veterans exposed to complex trauma post treatment. There was less evidence to draw on by comparison with studies that measured depression. However, EMDR and trauma-focused CBT were

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superior to control post treatment and were associated with large and positive effects in favour of reducing anxiety.

Childhood sexual abuse People exposed to childhood sexual abuse formed the next largest complex trauma subgroup. We showed that psychological interventions overall were associated with large and positive treatment effects for reducing PTSD in this subgroup post treatment only. As was the case with veterans, individual trauma-focused CBT was the most effective individual treatment for PTSD in people exposed to childhood sexual abuse. In addition, evidence gleaned from the non-RCTs showed that trauma-focused CBT was superior to control in reducing PTSD avoidance symptoms, suggesting that this approach was among the most effective in this group. Moreover, while single-component and trauma-focused interventions were collectively superior to control post treatment, it is clear that larger and positive effects were observed in trials that tested multicomponent and trauma-focused interventions in the childhood sexual abuse subgroup.

A similar pattern emerged for associated depression symptoms in this subgroup. When pooled together, psychological interventions in general were associated with large and positive effects for reducing depression post treatment; there was only modest evidence that these effects were positive at follow-up. Individual trauma-focused CBT and, collectively, single-component and trauma-focused interventions were superior to control for reducing depression post treatment. Consistent with the findings for veterans, the single-component and non-trauma-focused interventions were also superior to control post treatment for depression. Furthermore, the largest treatment effects for depression symptoms observed in the childhood sexual abuse subgroup were associated with multicomponent and trauma-focused interventions. With veteran and childhood sexual abuse being prototypical exposures for CPTSD, it might be that, among these populations, PTSD and associated depression symptoms are more effectively managed with multicomponent approaches that also include non-trauma-focused work. There was, however, no strong evidence in any direction for which types of psychological interventions might be most effective for reducing anxiety symptoms in this subgroup.

War-affected populations War-affected populations comprised the next largest subgroup. All analyses in this subgroup were conducted post treatment. Although psychological interventions of any type were superior to control for PTSD symptoms, the sizes of the SMDs were small in comparison with all other subgroups except for veterans. Individual trauma-focused CBT interventions were the most efficacious for reducing PTSD symptoms in war-affected populations. In addition, evidence gleaned from the non-RCTs showed that trauma-focused CBT was superior to control in reducing PTSD avoidance symptoms, suggesting that this approach was among the most effective in this group. Single-component and trauma-focused interventions were marginally more effective than multicomponent and trauma-focused interventions, but both approaches yielded medium and positive treatment effects in favour of reducing PTSD symptoms. Evidence from non-RCTs suggested that multicomponent interventions were in fact inferior to control for PTSD symptoms, but this finding was not endorsed by the meta-analyses of trials.

Comparable medium and positive treatment effects were observed for individual trauma-focused CBT in this subgroup for associated depression symptoms. Single-component, but not multicomponent, trauma-focused interventions were superior to control post treatment for depression symptoms. There was less evidence to judge the effectiveness of psychological interventions for anxiety symptoms in war-affected populations. Individual trauma-focused CBT was the only class of intervention associated with significant and positive effects in favour of reducing anxiety.

Refugees Few meta-analyses were possible among studies that included refugees. Any psychological intervention was vastly superior to control post treatment and also at follow-up for PTSD symptoms in refugees. In keeping with a recent review of treatments in refugees and asylum seekers,173 we found that very

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 73 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. DISCUSSION

large and positive treatment effects for PTSD were observed in studies that compared trauma-focused CBT and EMDR with control post treatment, but these effects were not sustained at follow-up. A similar picture was shown when psychological interventions were compared with control for associated depression symptoms: trauma-focused CBT and EMDR emerged as being better than control post treatment, but these findings were based on scarce evidence and it is not possible to judge if these effects are maintained at follow-up. Based on limited evidence from non-RCTs, it is possible that non-trauma-focused interventions could be effective for PTSD in refugees, but this finding was not observed in the meta-analyses of the trials. There was insufficient evidence to determine if psychological interventions were effective for anxiety symptoms in refugees.

Domestic violence There was very limited evidence to draw on to make firm conclusions about the effectiveness of psychological interventions in the subgroup of trials that included people exposed to domestic violence. Individual trauma-focused CBT was associated with very large and positive effects in favour of reducing PTSD and associated depression symptoms in this subgroup post treatment only. However, these findings were associated with high levels of uncertainty and based on few studies of variable quality.

Summary of results of pharmacological interventions The pooled results for pharmacological interventions in veterans showed that only antipsychotic medication was effective in reducing PTSD symptoms post treatment. The SMD for antipsychotics was equivalent to that observed in a comparable analysis in veterans that compared psychological interventions as a whole with control, but less than half the size of that observed in the analysis that compared multicomponent and trauma-focused interventions with control. There was also a small amount of evidence to signal that blood pressure medicine (prazosin) can reduce PTSD symptoms in veterans. Curiously, in veterans, antipsychotic medication was not effective in reducing symptoms of psychosis.

These findings might suggest that, in veterans at least, pharmacological interventions alone are not as effective as using multicomponent and trauma-focused interventions for PTSD symptoms. Moreover, additional strategies might be warranted to more effectively manage symptoms of psychosis in veterans in the presence of complex trauma.

Heterogeneity

The I2 statistic and chi-squared tests for the pooled results across all populations demonstrated substantial and significant heterogeneity at the 0.10 level for all classes of psychological interventions for PTSD symptoms. A similar picture was seen in the forest plots for the pooled results across all populations for associated symptoms of depression and anxiety. Although this might be mainly attributed to clinical diversity among the populations, it is also known that there is a link between meta-analysis size and heterogeneity levels and the high levels detected in our review might also thus be a function of the size of the review.

We explored these high levels of heterogeneity by undertaking subgroup analyses of the effectiveness of interventions by population. For the primary outcome, the pooled results for psychological interventions as a whole were associated with much less heterogeneity in the veteran and war-affected subgroups, with I2 results (between 42 and 50%) suggesting lower levels of between-study variability, but chi-squared results were still significant suggesting inconsistency between study results.

However, the pooled results for PTSD symptoms by intervention type among the veteran and war-affected subgroups returned considerably lower levels of heterogeneity. It might be that subgrouping by population and then by intervention appears to explain much of the heterogeneity in veteran and war-effected groups but not in others (e.g. childhood sexual abuse groups). This trend was not duplicated in the childhood

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sexual abuse subgroup, in which the pooled results across all psychological interventions and for specific classes of psychological interventions were still associated with high and significant levels of heterogeneity, making it more difficult to be confident about the true size and direction of effects in this subgroup. There was negligible and non-significant levels of heterogeneity for the pooled results for PTSD for all and any class of psychological intervention in the refugee and domestic violence subgroups. We might suggest that the lower and nil levels of heterogeneity returned in the subgroup analyses can partly be explained by less clinical variability and fewer trials within each subgroup. However, it is worth noting that, among the veteran, war-affected and childhood sexual abuse subgroups, heterogeneity was still more apparent in the pooled results that compared composite intervention categories with control. This was especially true for the pooled results that compared multicomponent and trauma-focused interventions with control and it might be that, in these analyses, heterogeneity was partly driven by variability among intervention components as well as by any residual clinical diversity.

In addition, we can conclude on the basis of the meta-regression results that population type partly moderated the effectiveness of psychological interventions for PTSD symptoms, with interventions doing less well in veterans and war-affected populations and significantly better in those exposed to domestic violence. In this sense, clinical diversity accounted for a modest amount of the heterogeneity observed in the pooled results across all populations, but there was still significant levels of residual heterogeneity that remained unexplained. Similarly, while the meta-regression was able to model the moderating effects of intervention content on the effectiveness for PTSD symptoms, results were fairly inconclusive, with the multivariable model that included only imaginal exposure and psychoeducation accounting for a fraction of heterogeneity and between-study inconsistencies.

Component network meta-analysis

We further explored the treatment effects of different components of the composite complex interventions included by using component network meta-analysis. The results of the component network meta-analysis showed that the components of standard trauma-focused CBT – cognitive restructuring, imaginal exposure and relaxation – appear to be effective for PTSD symptoms. This is consistent with the results of the population subgroup analyses. There were strong interaction effects between relaxation, cognitive restructuring and imaginal exposure in part because most of these components were used together.

Mindfulness was treated as a component and, in that sense, it was an approach identified in studies that primarily tested a mindfulness intervention as well as in studies in which mindfulness was a component of a broader CBT intervention. However, there were limitations to categorising mindfulness interventions owing to the variability of reporting, especially when mindfulness was but one of several components as part of a broader CBT package. There is scope here for future work to tease apart differences in the effectiveness of mindfulness when delivered as a stand-alone therapy and mindfulness as part of a composite psychological intervention.

The analyses of phase-based approaches presented even greater challenges. The phase-based approaches included in this review comprised combinations of multicomponent trauma-focused CBT, DBT, EMDR and IPT. Pragmatically, these approaches were categorised for the network meta-analysis in terms of the components included, for example imaginal exposure or mindfulness. However, we also coded these interventions as phased based if the components were phased in such a way that allowed for stabilisation before working on the trauma. It is unclear if the phasing itself constitutes an intervention or if it is a higher order theoretical construct, but phasing of these components, as well as the intervention content, appears to be one of the factors having an impact on effectiveness. There is a need for future work on phase-based approaches to reach a consensus on how phasing is conceptualised in the presence of composite interventions.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 75 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. DISCUSSION

Attrition

Across all populations, trauma-focused CBT was associated with reduced odds of attrition compared with control. There was less evidence to draw firm conclusions about the attrition rate for other interventions, although there was some suggestion that across all populations EMDR incurred a greater attrition rate than control. When attrition was analysed across population subgroups, we found that veterans who received any type of psychological intervention were half as likely to drop out than those on a waitlist or in the active control. In studies that tested psychological interventions in people exposed to childhood sexual abuse, the attrition rate for any psychological intervention was one-quarter of that observed in the control groups. There was a mixed picture among studies that included refugees, with some evidence that there were greater rates of attrition among those given a psychological intervention than in the control, suggesting that it is a challenge for displaced populations to adhere to psychological treatment protocols. Why this might be is not clear and future work could focus on the acceptability and feasibility of psychological interventions in this group. There was insufficient evidence to determine the odds of attrition in war-affected and domestic abuse populations.

Acceptability and feasibility of interventions: qualitative findings

The narrative synthesis of the subset of qualitative studies identified three core themes related to patient ratings about the acceptability and feasibility of interventions: therapeutic context, skills strengthening, and self-efficacy and reward. These themes cut across patient perceptions about both trauma- and non-trauma-focused therapies. Specifically, where and how interventions were delivered were seen to be important factors that determined acceptability and feasibility. Group delivery could be advantageous in some contexts, for example for the delivery of non-trauma-focused interventions such as mindfulness, but there were risks of vicarious re-traumatisation for those attending group-based therapies with a focus on trauma reprocessing. Perceptions about the acceptability of different therapeutic approaches were split between instrumental perceptions about the capacity for interventions to confer life skills and perceptions about how likely interventions were to aid symptomatic recovery. For those primarily engaged with non-trauma-focused interventions, there was a sense of these approaches equipping them with practical skills that made using other health- and social-care services more feasible. By contrast, among those who had experience of trauma-focused interventions, their willingness to persist with treatment was linked with their belief that they were going to feel better and the emergence of vital signs that were indeed feeling better.

Comparison with other reviews and guidance

We have shown that existing psychological treatments for PTSD are effective for people with a history of complex traumatic events. The strongest evidence was in favour of trauma-focused therapies such as trauma-focused CBT and EMDR delivered either as stand-alone therapies or as part of single-component and trauma-focused interventions. This finding mirrors that of a Cochrane review for psychological therapies for the treatment of chronic PTSD and is consistent with the NICE guideline that recommends the use of trauma-focused psychological treatment for PTSD for ≥ 3 months.20,174 While there was less good evidence in favour of non-trauma-focused interventions, we did show that IPT and mindfulness were effective, to varying degrees, across all populations for PTSD symptoms and to a lesser extent for depression too. This breaks with the NICE guideline, which suggests that non-trauma-focused interventions should not be routinely offered to people with chronic PTSD for > 3 months. We were not able to identify sufficient evidence about adverse events associated with psychological treatments to make judgements about the safety of these approaches in people with complex trauma. However, we showed that dropout was lower in people offered psychological interventions and this might suggest that existing trauma-focused interventions are at least acceptable and feasible, as well as effective, in the presence of complex trauma.

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Consistent with the International Society for Traumatic Stress Studies (ISTSS) expert consensus guidelines for CPTSD, we also showed that phase-based interventions that drew on a variety of trauma-focused (CBT, EMDR) and non-trauma-focused (DBT, IPT) approaches and included stabilisation and skills strengthening were effective across all populations for PTSD symptoms.175 However, unlike the ISTSS expert guidelines, our review includes only evidence from RCTs and we were able to also show that phasing of interventions moderated effectiveness, making our findings more robust and trustworthy.

Current NICE guidance suggests that, when several problems need to be addressed, especially in the presence of multiple traumatic events or when presented with comorbid problems, trauma-focused interventions should perhaps be extended and wrapped around a broader care plan. However, we showed that unmodified and existing trauma-focused treatments delivered individually or as part of multicomponent packages were also shown to be effective for managing associated symptoms of depression and anxiety in people exposed to complex trauma.

Although the underlying findings from the pooled results across all complex trauma populations show that trauma-focused interventions are effective for PTSD and associated mental disorder comorbidities, the effects were less pronounced in veterans and war-affected populations. A recent rapid review of service provision for UK armed forces veterans with PTSD included a meta-review of seven systematic reviews and concluded that there was limited and low-quality evidence in favour of EMDR, cognitive processing therapy, trauma-focused CBT and exposure-based therapies for PTSD symptoms and depression.176 In addition, this rapid review also found evidence in favour of a broad range of pharmacotherapies for PTSD and depression in veterans. Previous reviews have shown that SSRIs are superior to placebo for PTSD in a wide range of populations with PTSD, including those exposed to combat trauma.177 By contrast, our findings showed that only antipsychotics were effective for reducing PTSD symptoms in veterans, suggesting that pharmacotherapy might not be a candidate for first-line therapy in the presence of complex trauma.

Although adjacent to and in some senses part of the same broader class of people affected by humanitarian crises, we undertook separate subgroup analyses of war-affected populations and of refugees. Among the war-affected populations, we showed that trauma-focused CBT was effective for reducing PTSD but there was little support for other approaches. Similarly, Purgato et al.178 have shown in a Cochrane review that psychological therapies, many with a trauma focus, are effective at reducing PTSD among people affected by humanitarian crises. The pooled treatment effect for PTSD identified by Purgato et al.178 was twice that identified in our review and this might be accounted for by their exclusive focus on low- to middle-income countries and the inclusion of studies of children and adolescents. Our findings and those of Purgato et al.178 were very similar, however, when assessing the impact of psychological interventions on depression and anxiety in adults alone.

Dorrepaal et al.179 have previously shown that trauma-focused therapies, especially those that include exposure, can benefit people with a history of childhood sexual abuse. Of note in our review was that single-component and non-trauma-focused interventions were the most effective for associated depression symptoms among childhood sexual abuse populations, suggesting that different combinations of therapies that include non-trauma- as well as trauma-focused approaches might be warranted in this population.

Among refugees and asylum seekers resettled in high-income countries, manualised and brief narrative exposure therapies based on CBT have been shown to be effective for PTSD symptoms.180 There is a strong argument that treatment provision for conflict-affected and displaced populations should be provided as part of multiagency care and extend beyond PTSD symptoms.181 In the absence of such integrated and multiagency care, our review at least confirms that trauma-focused interventions are superior to control for PTSD and can also be effective for depression too.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 77 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. DISCUSSION

A review based on 21 studies (11 of which measured PTSD) showed that brief psychological interventions that are tailored to meet the additional needs of people exposed to intimate partner domestic violence are effective for PTSD, depression, increased self-esteem and functioning.182 The most effective classes of interventions were CBT and IPT. Our findings partially concur, but are based on a very narrow and limited data set drawn from few studies. In the light of the thin evidence base, there is a consensus that further well-designed and controlled studies of the effectiveness of interventions for survivors of intimate partner violence are needed, especially with a focus on how setting moderates effectiveness.

There was a less clear picture about the effectiveness of treatments for the CPTSD symptom cluster. Conventional stand-alone trauma-focused interventions were not effective in treating emotional dysregulation or interpersonal problems, but did have a positive impact on negative self-concept. In keeping with the ISTSS expert consensus guidelines for CPTSD, we identified phase-based approaches as a leading candidate intervention for managing emotional dysregulation, although the evidence was based on only three trials and the result was of borderline significance. More robust evidence was gleaned from the component network meta-analysis, which identified phasing as a key moderating component of the effectiveness of both trauma- and non-trauma-focused interventions.

Taken together, the fact that trauma-focused interventions do less well in certain populations with complex trauma, and only have a modest impact on disturbances of self-organisation, suggests that our review findings endorse the current diagnostic distinction between CPTSD and PTSD. This is an important argument that has implications for research and practice. We explicitly eschewed a diagnostic approach to the inclusion of studies in this review, but, nonetheless, we would suggest that our findings converge with comparable reviews that have opted to use the new ICD-11 diagnostic CPTSD category as an organising feature of their inclusion criteria.183 Accordingly, because CPTSD exerts symptoms over and above PTSD extending to disturbances of self-organisation, there is merit in exploring ways to harness existing trauma- and non-trauma-focused interventions more effectively, with phase-based interventions among the leading candidate approaches.

Strengths and limitations

Our review has a number of strengths that enhance the robustness of the findings. By taking a non-diagnostic approach, we were able to develop and operationalise broad inclusion criteria for the population of interest based on exposure to traumatic events that could be defined as complex using the ICD-11 criteria for CPTSD, but which need not have been diagnosed as CPTSD. In doing so, our search was not tied to a narrowly defined group of studies that exclusively evaluated interventions in populations with the as yet untested diagnostic label of CPTSD, but rather captured a broader set of studies salient to more complex trauma rather than a single event and not of an interpersonal nature. In addition, our approach conferred a level of scientific independence from the clinical community actively involved in research in CPTSD and, as such, we feel confident that the process of screening and inclusion was as free from bias as possible. However, to ensure that our review linked with but did not duplicate other ongoing evidence syntheses in the field, we convened a study advisory group that included content and clinical experts in chronic PTSD and CPTSD. The advisory group offered indispensable advice about how to ensure that our review retained an independent identity outside existing evidence syntheses on CPTSD, provided scientific scrutiny about the process of the review, and supported and enabled dissemination activities within the broader trauma studies community.

Our broad approach also extended to including both randomised and non-randomised evaluations of psychological interventions, evaluations of pharmacological interventions and qualitative evaluations of acceptability of interventions, making this review the largest and most comprehensive assessment of treatment effectiveness and acceptability of interventions in complex trauma. This approach was facilitated by conducting an extensive search across key electronic databases, as well as searching

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

specialist fee-for-service libraries and hand searching existing systematic reviews. Although we did not double screen all titles and abstracts, we did run a pilot screening exercise whereby members of the research team double screened a sample of abstracts and titles to familiarise themselves with the PICO. At the title and abstract screening phase, all uncertain decisions were resolved by a consensus meeting, thus minimising the risk of excluding relevant studies.

Additional strengths of the review include the application of robust and innovative approaches to understanding treatment effectiveness and moderators of effectiveness. We not only completed a broad range of meta-analyses, including subgroup analyses by population, but also explored moderators using multivariable meta-regression. By searching extensively and adopting a broad approach to inclusion, we were able to assemble a much larger data set than in previous reviews, enhancing our ability to quantify and explore heterogeneity with a greater level of statistical power and reducing the chance of spurious findings.184 Many of the meta-analyses exhibited high levels of estimated heterogeneity, but this is a positive finding, as it appears that heterogeneity levels are being consistently underestimated in meta-analyses.185 Because there is a link between meta-analysis size and heterogeneity levels, we anticipated that we might detect high levels given the size of our review, but the large between-study variability suggests that there might be other study- or patient-level variables that could explain some of it. Individual patient data meta-analysis is likely to confer considerable advantages to accounting for such residual heterogeneity associated with patient-level characteristics.

We were not able to fully undertake all planned PPI activities as specified in the protocol. Specifically, we were unable to recruit service users with experience of complex trauma to join the study advisory group. Our initial plan was to use The Retreat hospital in York to identify eligible candidates for the advisory group, but the length of time that elapsed between applying for and securing research governance permissions meant that opportunities to do this were prohibitively curtailed. However, during this down time, we worked with the Involvement Lead and Iram Shah from The Retreat to offer experts by experience from a voluntary organisation run by service users for people affected by mental health problems to contribute to a series of telephone and face-to-face focus groups. These groups, in lieu of lay membership of the advisory group, contributed critical thinking about the focus of our review and generated data that informed the scope of the research prioritisation exercise. In addition, via our network with the Tees, Esk and Wear Valleys NHS Foundation Trust, we invited service users by experience (as well as key stakeholders from the scientific and clinical communities with an interest in trauma and stress research) to attend and contribute to the research prioritisation day. We also engaged a wider group of stakeholders and service users in the research prioritisation exercise via our social media presence. In these ways, we were still able to build PPI into our review in ways that aligned with established best practice for user involvement in systematic reviews.186

We originally committed to using the ROBINS-I40 tool for assessing the risk of bias in non-RCTs, but ultimately we opted for a more parsimonious approach afforded by a quality appraisal checklist widely used by NICE in public health guidelines. Although the ROBINS-I tool has emerged as the most likely gold standard method for assessing the risk of bias in non-randomised studies of interventions, it was decided that the tool operated at too high a level of resolution for the purposes of our review and the resource needed to use this tool appropriately would have outstripped capacity within the team at a time when the emphasis was on data extraction and assessing the risk of bias in over 100 RCTs. Future studies that intend on including both non-RCTs and RCTs should ensure that there is sufficient capacity within the review team to use the ROBINS-I tool.

Despite using an extensive search strategy and applying broad inclusion criteria, there is an under- representation of studies in our review with a focus on complex trauma populations drawn from prison settings and survivors of torture and forced migrant labour, otherwise known as modern slavery. Future work should look to identify ways to ensure these populations are not overlooked. In addition, our search did not capture a critical mass of studies that included outcomes related to comorbid psychiatric states such as borderline personality disorder. This might have been off set had we adopted

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 79 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. DISCUSSION

a more clinical and diagnostic approach to our inclusion criteria, but we have previously explained that our review set out to explicitly avoid running searches around diagnostic labels. Finally, while we did include populations with comorbidities, including psychiatric disorders and common mental health problems, we excluded those with dual diagnosis of complex trauma and substance and alcohol misuse on the grounds that these populations are likely to require care that is different from and more specialist than that typically provided in the context of PTSD. However, recent work among ex-serving regular personnel deployed to combat roles in Iraq or Afghanistan has highlighted that populations with dual diagnoses (e.g. mental health problems and alcohol misuse) are an important feature following exposure to complex trauma.187

A further limitation relates to the use of standard frequentist approaches to random-effects meta- analyses. When there are few studies included in the meta-analyses, there is the potential for bias in estimating the heterogeneity parameter.

Conclusions and implications for research

The funder called for a review to identify the most promising front runners that the Health Technology Assessment programme could then consider for future primary research in complex trauma as part of a separate call.

We have identified that trauma-focused CBT and other trauma-focused interventions, including EMDR, delivered as single-component or multicomponent approaches are superior to control for PTSD symptoms and associated mental comorbidities. However, the size of these positive treatment effects was not equivalent across populations exposed to complex trauma, with treatments being least effective among veterans. Phase-based interventions, along with non-trauma-focused intervention components including mindfulness and relaxation, are potentially among the most effective approaches for PTSD symptoms in people with a history of complex trauma, such as childhood sexual abuse. In addition, there was inconclusive evidence that existing trauma-focused interventions are effective in treating the symptom cluster associated with disturbances of self-organisation typically seen in CPTSD. There is scope to identify if phase-based approaches are more effective than non-phase-based approaches for PTSD and the broader symptom profile associated with complex trauma. There was little evidence of effectiveness of pharmacological interventions for PTSD or for associated mental comorbidities, and no trial that tested the effectiveness of pharmacological interventions for outcomes related to disturbances of self-organisation.

Going forward, we can synthesise the findings from our meta-analyses and from the stakeholder and service user research prioritisation event and draw up a long-list of research questions for consideration in future funding calls. These research questions come under five main topic domains: (1) the effectiveness of psychological and/or pharmacological interventions, (2) the process and implementation of care, (3) understanding the lived experience of complex trauma, (4) the safety and adverse event profile of interventions and (5) methodological considerations about trials in complex trauma.

1. studies about the effectiveness of interventions

¢ definitive and fully powered evaluations of the effectiveness of interventions in complex trauma with long-term follow-up (i.e. at least 12 months), especially in veterans, childhood sexual abuse populations and populations affected by humanitarian crises

¢ phase-based versus non-phase-based interventions ¢ trauma-focused versus non-trauma-focused interventions (including IPT, DBT, mindfulness and relaxation) ¢ integrated and multiagency care packages versus control ¢ pharmacological interventions versus placebo.

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

2. studies about the process and implementation of care

¢ qualitative and quantitative process evaluations that draw on best practice for understanding the relationship between intervention and programme theory and anticipated outputs and trial results (Medical Research Council guidance)

¢ measuring fidelity and adherence to interventions ¢ understanding if contexts (e.g. setting, timing of delivery) moderate outcomes ¢ assessing what was delivered (i.e. intervention content) and how it was delivered (e.g. individual vs. group) with a view to drawing conclusions about drivers of effectiveness

¢ qualitative evaluations of the acceptability and feasibility of interventions among people exposed to complex interventions to inform barriers to and facilitators of treatment uptake, especially in refugees and asylum seekers.

3. studies about understanding the lived experience of people with a history of complex trauma

¢ qualitative evaluations that draw on a phenomenological perspective to elicit in-depth narratives of the day-to-day lived experience of people with a history of complex trauma ¢ ethnographic research to illustrate commonalities and differences in the lived experience of complex trauma across population subgroups.

4. studies about the safety and adverse event profile of interventions for people with a history of complex trauma

¢ evaluations of adverse events associated with trauma- and non-trauma-focused psychological interventions (e.g. rates of re-traumatisation) ¢ evaluations of adverse events associated with pharmacological treatments in all complex trauma populations.

5. studies about methodological considerations in trials among people with a history of complex traumatic events

¢ developing a core outcome set for trials in complex trauma that include outcomes related to disturbances of self-organisation and mental comorbidities ¢ testing the validity of the new ICD-11 diagnostic category for CPTSD to identify and recruit eligible participants to experimental studies.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 81 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Acknowledgements

Contributions of authors

Hollie Melton (https://orcid.org/0000-0003-3837-510X) (Research Fellow, evidence synthesis) screened titles, abstracts and full-text papers, led the data extraction and risk-of-bias assessment, undertook attrition meta-analyses, led the writing up of the risk-of-bias assessment for randomised controlled intervention studies and non-randomised controlled intervention studies, led the synthesis of non-randomised intervention studies, led the research prioritisation exercise and ran the INCiTE social media account.

Nick Meader (https://orcid.org/0000-0001-9332-6605) (Research Fellow, evidence synthesis and statistics) contributed to the research prioritisation exercise, was principally responsible for the methodological aspects of the effectiveness review and led the meta-analyses, meta-regression and component network meta-analysis.

Holly Dale (https://orcid.org/0000-0002-6553-7939) (Research Training Fellow, evidence synthesis) screened titles, abstracts and full-text papers, contributed to the research prioritisation exercise, contributed to data extraction and contributed to writing up the risk-of-bias assessment for randomised controlled intervention studies.

Kath Wright (https://orcid.org/0000-0002-9020-1572) (Information Service Manager, Information Specialist) was principally responsible for compiling and running database searches and building and maintaining the EndNote libraries.

Julie Jones-Diette (https://orcid.org/0000-0003-1769-8612) (Research Fellow, evidence synthesis and PROSPERO manager) contributed to the research prioritisation exercise and led the data extraction and appraisal of qualitative data.

Melanie Temple (https://orcid.org/0000-0002-4496-3437) (Consultant Psychiatrist, complex trauma) contributed to the research prioritisation exercise, data extraction and meta-analyses of phase-based interventions.

Iram Shah (https://orcid.org/0000-0002-7868-601X) (Consultant Trauma Psychotherapist, trauma) contributed to the research prioritisation exercise, led the service user engagement, ran the focus groups to support delivery of the PPI strategy and led the writing up of the focus group results.

Karina Lovell (https://orcid.org/0000-0001-8821-895X) (Professor of Mental Health, psychological therapies and PPI) contributed to the research prioritisation exercise and supported the development of the PPI engagement strategy.

Dean McMillan (https://orcid.org/0000-0002-2901-8410) (Reader, mental health services research) contributed to intervention coding, meta-analyses and protocol development.

Rachel Churchill (https://orcid.org/0000-0002-1751-0512) (Professor of Evidence Synthesis, knowledge mobilisation) contributed to the research prioritisation exercise and was a full member of the study advisory group.

Corrado Barbui (https://orcid.org/0000-0003-1073-9282) (Professor of Psychiatry, psychiatry and global mental health) contributed to writing the protocol and search terms and to identifying ongoing studies.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 83 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. ACKNOWLEDGEMENTS

Simon Gilbody (https://orcid.org/0000-0002-8236-6983) (Professor of Health Services Research, psychological medicine) contributed to writing the protocol and the research prioritisation exercise.

Peter Coventry (https://orcid.org/0000-0003-0625-3829) (Senior Lecturer, health services research) had overall responsibility for the project, chaired the review group meetings, was a full member of the advisory group, supervised the review team, contributed to the research prioritisation exercise and took primary responsibility for the drafting of the report.

All authors contributed to the report and approved the final version.

Contributions of others

We would like to express our gratitude to the members of the study advisory group – Professor Jon Bisson (Cardiff University), Professor Thanos Karatzias (Edinburgh Napier University), Dr Marylene Cloitre (New York University School of Medicine) and Dr Neil Roberts (Cardiff University) – for their support and contribution to undertaking this review. Their top-rate critical thinking and wealth of knowledge in the field of trauma studies has been immensely helpful to the review team and our approach to this review has been significantly improved by their guidance. Any errors or omissions in the review are, however, the responsibility of the review team and not the study advisory group.

We thank Dr Jane Dalton (previously of the Centre for Reviews and Dissemination, University of York) for her contributions to screening and data extraction and we also want to thank Gary Raine (the Centre for Reviews and Dissemination, University of York) for early work on the qualitative acceptability review.

We also thank all contributors to the research prioritisation exercise: Professor Joe Reilly [Tees, Esk and Wear Valleys NHS Foundation Trust (TEWV)], Lindsay Jones (TEWV), Simon Hughes (TEWV), Amanda Hall (TEWV), Madeleine Rowlinson (TEWV), Dr Mark McFetridge (The Retreat, York), Emily Herbert (The Retreat, York), Trish Horner (Independent Domestic Abuse Services, York), Dr Dominic Murphy (Combat Stress/King’s College London), Maria O’Keefe (Home-Start, York) and Debra Hilton (Home-Start, York). Special thanks go to Vanessa Garrity (Beyond The Room) for facilitating the event and promoting INCiTE on social media and to André Tomlin (The Mental Elf/Beyond The Room) for providing support via The Mental Elf and organising the format of the prioritisation day and the online voting.

Publication

Coventry P, Meader N, Melton H, Temple M, Dale H, Wright K, et al. Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: systematic review and component network meta-analysis. PLOS Med 2020;17:e1003262.

Data-sharing statement

All data requests should be submitted to the corresponding author for consideration. Access to anonymised data may be granted following review.

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

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© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 85 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. REFERENCES

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© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 117 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. REFERENCES

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© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 119 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 1 Literature search strategies for the effectiveness review

iterature searches of the following databases were conducted: CINAHL, CENTRAL, EMBASE, LInternational Pharmaceutical Abstracts, MEDLINE, PILOTS, PsycINFO and Science Citation Index.

The original searches carried out in April and May 2017 identified 17,177 records, which were downloaded, imported into EndNote bibliographic software and de-duplicated to leave 10,212 unique records.

CINAHL via EBSCOhost

Search date: 20 April 2017.

Records retrieved: 1919.

Date range searched: 1937 onwards.

TABLE 15 Search strategy for CINAHL via EBSCOhost

Search terms Search options

S1 (MH “Violence”) OR (MH “Exposure to Violence”)

S2 TX violence

S3 (MH “Domestic Violence”) OR (MH “Intimate Partner Violence”) OR (MH “Dating Violence”)

S4 TX (batter$ N2 (wife* or wive* or woman or women or men or husband* or partner*)) OR TX (physical* N2 (abus* or assault* or violen* or aggress*)) OR TX emotional N2 abus*

S5 (MH “Rape”)

S6 TX rape OR TX (sexual* N2 (assault* or abus* or violen* or aggress*))

S7 (MH “Child Abuse, Sexual”) OR (MH “Child Abuse Survivors”) OR (MH “Sexual Abuse”) OR (MH “Child Abuse”)

S8 TX “child* sexual abuse”

S9 TX child* N2 exploit* OR TX child* N2 neglect* OR TX child* N2 trauma* OR TX (“non accidental injur*” or “non-accidental injur*” or “nonaccidental injur*”)

S10 TX “human rights abuse*”

S11 (MH “Human Trafficking”)

S12 TX ((human or person* or people) N2 (traffick* or exploit*)) OR TX ((forced or exploit*) N2 labour*)

S13 organ N2 traffick*

S14 TX slavery or slaves or “slave trade” S15 (MH “Torture”) OR (MH “Torture Survivors”)

S16 (MH “Prostitution”)

S17 TX (prostitut* or brothel*) OR TX (sex* N2 (exploit* or traffick*))

S18 (MH “Terrorism”)

S19 TX (terrorism or terrorist*) OR TX “political terror*” continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 121 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 15 Search strategy for CINAHL via EBSCOhost (continued)

Search terms Search options

S20 (MH “War”) OR (MH “War Crimes”)

S21 (MH “Holocaust”)

S22 TX ethnic* N2 cleans* OR TX genocide OR TX (civil N2 (unrest or conflict* or disturb* or war or wars or warfare)) OR TX (persecution or victimisation or victimization) OR TX (captivity or imprison*) OR TX concentration camp*

S23 (MH “Disasters”) OR (MH “Natural Disasters”) OR (MH “Mass Casualty Incidents”) S24 catastrophe* or (“catastrophic event*”)or(“catastrophic experience*”)

S25 (MH “Survivors+”)

S26 (MH “Refugees”)

S27 TX refugee* OR TX “asylum seek*” OR TX migrant* OR TX ((forcibly or internally) N2 displaced) OR TX (displace* N2 (people or person* or civilian*))

S28 (MH “Crime Victims”) OR (MH “Victims”)

S29 (MH “Prisoners”)

S30 (MH “Veterans”)

S31 TX ((expose* or exposure) N2 (abuse or assault* or disaster* or terror* or torture* or trauma* or rape or violen* or war or warfare)) OR TX (survivor* N2 (abuse or assault* or disaster* or terror* or torture* or trauma* or rape or violen* or war or warfare)) OR TX (victim* N2 (abuse or assault* or crime or disaster* or rape or terror* or torture* or trauma* or violen* or war or warfare)) OR TX (witness* N2 (abuse or assault* or disaster* or rape or terror* or torture* or trauma* or violen* or war or warfare))

S32 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 (143,422)

S33 (MH “Stress Disorders, Post-Traumatic+”)

S34 TX (PTSD or CPTSD) OR TX posttrauma* OR TX post-trauma* OR TX “post trauma*” OR TX “post traumatic stress” OR TX “combat stress*” OR TX “combat disorder*” OR TX DESNOS OR TX “complex trauma*” OR TX complex N3 trauma* OR TX “traumatic stress” OR TX “traumatic memor*”

S35 TX traumatisation OR TX traumatization OR TX (trauma* N3 (expos* or event* or experienc*))

S36 S33 OR S34 OR S35 (28,298)

S37 (MH “Cognitive Therapy+”)ORTX“cognitive behaviour* therap*” OR TX “cognitive behavior* therap*” OR TX “cognitive restructuring” OR TX “cognitive rescripting” OR TX “cognitive processing therap*” OR TX (CPT or CBT or TFCBT) OR TX “cognitive therap*” OR TX “cognitive behavioural treat*” OR TX “cognitive behavioral treat*” OR TX “cognitive trauma therap*” OR TX “trauma focus* CBT”

S38 (MH “Behavior Therapy”) OR TX (behavior* N2 (therap* or treat* or modif*)) OR TX (behavior* N2 (therap* or treat* or modif*)) OR TX ((dialectical behavio*) N1 (therap* or treat*)) OR TX (biofeedback or neurofeedback or (“sensory feedback”)) OR TX psychological N2 desensiti#ation OR TX (“eye movement desensiti#ation reprocessing”) OR TX EMDR OR TX (exposure N1 (therap* or treat*)) OR TX “live exposure” OR TX “imaginal exposure” OR TX “prolonged exposure therapy”

S39 TX “imaginal flooding” OR TX “exposure inhibition therap*” OR TX “implosive therap*” OR TX “image habituation” OR TX “inoculation training”

S40 ((MH “Acceptance and Commitment Therapy”)) OR TX acceptance N2 therap* OR TX commitment N2 therap* S41 (MH “Biofeedback”)

S42 (MH “Feedback”)

S43 (MH “Eye Movement Desensitization and Reprogramming”)

S44 (MH “Virtual Reality Exposure Therapy”)

S45 (MH “Hypnosis”)

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TABLE 15 Search strategy for CINAHL via EBSCOhost (continued)

Search terms Search options

S46 TX hypnosis or hypnotherap*

S47 (MH “Mindfulness”)

S48 TX mindfulness

S49 TX “supportive therap*” OR TX (non-directive N1 (counselling or counseling)) OR TX ((non directive) N1 (counselling or counseling))

S50 ((MH “Psychotherapy”) OR (MH “Psychotherapy, Brief”) OR (MH “Psychotherapy, Group”)OR (MH “Psychotherapy, Psychodynamic”)) OR TX psychodynamic N1 therap* OR TX “inter personal psychotherap*” OR TX “interpersonal psychotherap*” OR TX IPT OR TX “compassion therap*” OR TX “accelerated resolution*” OR TX “sensorimotor therap*” OR TX “schema therap*” OR TX stress N2 manag*

S51 (MH “Counseling”)ORTX“non-directive counsel*” OR TX “non directive counsel*” OR TX “nondirective counsel*” OR “compassion therap*”

S52 S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR S51 (99,780)

S53 ((MH “Hypnotics and Sedatives”)) OR TX (alprazolam or amobarbital or azaperone or barbital or bromisovalum or “chloral hydrate” or chloralose or chlordiazepoxide or chlormethiazole or dexmedetomidine or diazepam or diphenhydramine or eszopiclone or ethchlorvynol or etomidate or etorphine or flurazepam or glutethimide or hexobarbital or lorazepam or medazepam or medetomidine or mephobarbital or meprobamate or methapyrilene or methaqualone or midazolam or nitrazepam or oxazepam or paraldehyde or pentobarbital or phenobarbital or propofol or secobarbital or temazepam or thiamylal or thiopental or xylazine) OR TX “z drugs”

S54 (MH “Antianxiety Agents+”) OR (bromazepam or buspirone or chlormezanone or “clorazepate dipotassium” or estazolam or flunitrazepam or fluvoxamine or nordazepam or ondansetron or oxprenolol or prazepam or pregabalin or ritanserin or tranylcypromine or trazodone or triazolam or zolazepam or benzodiazepines or benzodiazepinones or “sedative antihistamine*” or promethazine)

S55 (MH “Antidepressive Agents+”) OR TX (benactyzine or clorgyline or deanol or “desvenlafaxine succinate” or “duloxetine hydrochloride” or iproniazid or isocarboxazid or “lithium carbonate” or “lithium compounds” or moclobemide or nialamide or phenelzine or pizotyline or rolipram or sertraline or tranylcypromine or “vilazodone hydrochloride” or Imipramine or mirtazapine)

S56 (MH “Antipsychotic Agents+”) OR TX (acepromazine or aripiprazole or azaperone or benperidol or butaclamol or chlorpromazine or chlorprothixene or clopenthixol or clozapine or droperidol or etazolate or flupenthixol or fluphenazine or fluspirilene or haloperidol or loxapine or “lurasidone hydrochloride” or mesoridazine or methiothepin or methotrimeprazine or molindone or ondansetron or “paliperidone palmitate” or penfluridol or perazine or perphenazine or pimozide or prochlorperazine) OR TX (promazine or “quetiapine fumarate” or raclopride or remoxipride or reserpine or risperidone or ritanserin or spiperone or sulpiride or thioridazine or thiothixene or “tiapride hydrochloride” or trifluoperazine or trifluperidol or triflupromazine or olanzapine) S57 (MH “Anticonvulsants+”) OR TX (anticonvulsants or acetazolamide or bromides or carbamazepine or clonazepam or “clorazepate dipotassium” or diazepam or dimethadione or estazolam or ethosuximide or flunarizine or lorazepam or “magnesium sulfate” or medazepam or mephenytoin or mephobarbital or meprobamate or nitrazepam or paraldehyde or phenobarbital or phenytoin or pregabalin or primidone or riluzole or thiopental or tiletamine or trimethadione or “valproic acid” or vigabatrin)

S58 (MH “Antimanic Agents+”)ORTX(“lithium chloride” or “lithium compounds” or lamotrigine or topiramate) S59 (MH “Monoamine Oxidase Inhibitors+”) OR TX (chlorphenamidine or clorgyline or cuprizone or furazolidone or harmaline or harmine or isocarboxazid or moclobemide or monocrotophos or pargyline or selegiline or tranylcypromine or Prazosin or N-Methyl-3,4-methylenedioxyamphetamine or MDMA or ecstasy)

S60 S53 OR S54 OR S55 OR S56 OR S57 OR S58 OR S59 (68,988)

S61 S32 AND S36 AND S52 (1786) S62 S32 AND S36 AND S60 (229)

S63 S61 OR S62 (1936)

S64 S61 OR S62 (1919) 1992 ONWARDS

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 123 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

CENTRAL via The Cochrane Library

Search date: 21 April 2017.

Records retrieved: 637.

Date range searched: from inception.

TABLE 16 Search strategy for CENTRAL via The Cochrane Library

#1 MeSH descriptor: [Violence] explode all trees #2 violence:ti,ab,kw (Word variations have been searched)

#3 MeSH descriptor: [Domestic Violence] explode all trees

#4 MeSH descriptor: [Intimate Partner Violence] explode all trees

#5 MeSH descriptor: [Battered Women] explode all trees

#6 batter* near/2 (wife* or wive* or woman or women or men or husband* or partner*):ti,ab,kw (Word variations have been searched)

#7 physical* near/2 (abus* or assault* or violen* or aggress*):ti,ab,kw (Word variations have been searched)

#8 emotional* near/2 abus*:ti,ab,kw (Word variations have been searched)

#9 MeSH descriptor: [Rape] explode all trees

#10 rape:ti,ab,kw or sexual* near/2 (abus* or assault* or violen* or aggress*):ti,ab,kw (Word variations have been searched)

#11 MeSH descriptor: [Child Abuse, Sexual] explode all trees

#12 child* sexual abuse:ti,ab,kw (Word variations have been searched)

#13 child* near/2 (exploit* or neglect* or trauma*):ti,ab,kw (Word variations have been searched) #14 non accidental injur*:ti,ab,kw or non-accidental injur*:ti,ab,kw or nonaccidental injur*:ti,ab,kw (Word variations have been searched)

#15 MeSH descriptor: [Human Rights Abuses] explode all trees

#16 MeSH descriptor: [Human Trafficking] explode all trees #17 (human or person or people) near/2 (traffick* or exploit*):ti,ab,kw (Word variations have been searched)

#18 (forced or exploit*) near/2 labour:ti,ab,kw (Word variations have been searched)

#19 MeSH descriptor: [Organ Trafficking] explode all trees

#20 MeSH descriptor: [Slavery] explode all trees

#21 MeSH descriptor: [Torture] explode all trees

#22 slavery or enslave* or torture*:ti,ab,kw (Word variations have been searched)

#23 MeSH descriptor: [Sex Workers] explode all trees #24 MeSH descriptor: [Prostitution] explode all trees

#25 prostitut* or brothel*:ti,ab,kw (Word variations have been searched)

#26 sex* near/2 (exploit* or traffick*):ti,ab,kw (Word variations have been searched)

#27 MeSH descriptor: [Terrorism] explode all trees

#28 terrorism or terrorist*:ti,ab,kw (Word variations have been searched)

#29 political terror*:ti,ab,kw (Word variations have been searched)

#30 MeSH descriptor: [Torture] explode all trees

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TABLE 16 Search strategy for CENTRAL via The Cochrane Library (continued)

#31 MeSH descriptor: [Warfare] explode all trees #32 MeSH descriptor: [Armed Conflicts] explode all trees

#33 MeSH descriptor: [War Crimes] explode all trees

#34 MeSH descriptor: [Genocide] explode all trees

#35 MeSH descriptor: [Holocaust] explode all trees

#36 MeSH descriptor: [Ethnic Cleansing] explode all trees

#37 civil near/2 (unrest or conflict* or disturbance* or war or wars or warfare):ti,ab,kw (Word variations have been searched)

#38 persecution or victimization or victimisation:ti,ab,kw (Word variations have been searched)

#39 captivity or imprison* or concentration camp*:ti,ab,kw (Word variations have been searched)

#40 MeSH descriptor: [Disasters] explode all trees

#41 MeSH descriptor: [Earthquakes] explode all trees #42 MeSH descriptor: [Tsunamis] explode all trees

#43 natural disaster*:ti,ab,kw (Word variations have been searched)

#44 earthquake* or tsunami*:ti,ab,kw (Word variations have been searched)

#45 humanitarian near/1 (crisis or crises):ti,ab,kw (Word variations have been searched)

#46 catastrophe* or catastrophic event* or catastrophic experience*:ti,ab,kw (Word variations have been searched)

#47 MeSH descriptor: [Survivors] explode all trees

#48 MeSH descriptor: [Refugees] explode all trees #49 asylum seeker* or refugee* or migrant*:ti,ab,kw (Word variations have been searched)

#50 (forcibly or internally) near/2 displace*:ti,ab,kw (Word variations have been searched)

#51 displace* near/2 (people or person* or civilian*):ti,ab,kw (Word variations have been searched)

#52 MeSH descriptor: [Crime Victims] explode all trees

#53 MeSH descriptor: [Adult Survivors of Child Abuse] explode all trees

#54 MeSH descriptor: [Disaster Victims] explode all trees

#55 MeSH descriptor: [Prisoners] explode all trees #56 MeSH descriptor: [Prisoners of War] explode all trees

#57 MeSH descriptor: [Slaves] explode all trees

#58 MeSH descriptor: [Veterans] explode all trees

#59 MeSH descriptor: [Military Personnel] explode all trees

#60 exposure near/2 (abuse or assault* or disaster* or terror* or torture* or trauma* or rape or violen* or war or warfare):ti,ab,kw (Word variations have been searched)

#61 exposed near/2 (abuse or assault* or disaster* or terror* or torture* or trauma* or rape or violen* or war or warfare):ti,ab,kw (Word variations have been searched) #62 survivor* near/2 (abuse or assault* or disaster* or terror* or torture* or trauma* or rape or violen* or war or warfare):ti,ab,kw (Word variations have been searched)

#63 victim* near/2 (abuse or assault* or crime or disaster* or rape or terror* or torture* or trauma* or violen* or war or warfare):ti,ab,kw (Word variations have been searched)

#64 witness* near/2 (abuse or assault* or disaster* or rape or terror* or torture* or trauma* or violen* or war or warfare):ti,ab,kw (Word variations have been searched) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 125 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 16 Search strategy for CENTRAL via The Cochrane Library (continued)

#65 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48 or #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56 or #57 or #58 or #59 or #60 or #61 or #62 or #63 or #64

#66 MeSH descriptor: [Stress Disorders, Post-Traumatic] explode all trees #67 PTSD or CPTSD:ti,ab,kw (Word variations have been searched)

#68 posttrauma*:ti,ab,kw (Word variations have been searched)

#69 post-trauma*:ti,ab,kw (Word variations have been searched)

#70 post trauma*:ti,ab,kw (Word variations have been searched)

#71 “post traumatic stress”:ti,ab,kw (Word variations have been searched)

#72 combat stress:ti,ab,kw (Word variations have been searched)

#73 combat disorder*:ti,ab,kw (Word variations have been searched) #74 DESNOS:ti,ab,kw (Word variations have been searched)

#75 extreme distress:ti,ab,kw (Word variations have been searched)

#76 complex near/3 trauma:ti,ab,kw (Word variations have been searched)

#77 traumatic stress:ti,ab,kw (Word variations have been searched)

#78 traumatic memories:ti,ab,kw (Word variations have been searched)

#79 traumatization:ti,ab,kw (Word variations have been searched)

#80 “traumatisation”:ti,ab,kw (Word variations have been searched)

#81 trauma near/3 (expos* or event* or experienc*):ti,ab,kw (Word variations have been searched) #82 #66 or #67 or #68 or #69 or #70 or #71 or #72 or #73 or #74 or #75 or #76 or #77 or #78 or #79 or #80 or #81

#83 #65 and #82

#84 MeSH descriptor: [Cognitive Therapy] explode all trees

#85 cognitive near/2 therap*:ti,ab,kw (Word variations have been searched)

#86 “cognitive restructuring”:ti,ab,kw (Word variations have been searched)

#87 cognitive rescripting:ti,ab,kw (Word variations have been searched)

#88 “cognitive processing therapy”:ti,ab,kw (Word variations have been searched) #89 CPT:ti,ab,kw (Word variations have been searched)

#90 cognitive near/2 treat*:ti,ab,kw (Word variations have been searched)

#91 CBT or TFCBT:ti,ab,kw (Word variations have been searched)

#92 MeSH descriptor: [Behavior Therapy] explode all trees

#93 behavior* near/2 (therap* or treat* or modif*):ti,ab,kw (Word variations have been searched)

#94 behaviour* near/2 (therap* or treat* or modif*):ti,ab,kw (Word variations have been searched)

#95 MeSH descriptor: [Biofeedback, Psychology] explode all trees #96 MeSH descriptor: [Feedback, Sensory] explode all trees

#97 MeSH descriptor: [Neurofeedback] explode all trees

#98 biofeedback:ti,ab,kw (Word variations have been searched)

#99 “neurofeedback”:ti,ab,kw (Word variations have been searched)

#100 “sensory feedback”:ti,ab,kw (Word variations have been searched)

#101 MeSH descriptor: [Eye Movement Desensitization Reprocessing] explode all trees

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TABLE 16 Search strategy for CENTRAL via The Cochrane Library (continued)

#102 MeSH descriptor: [Implosive Therapy] explode all trees #103 MeSH descriptor: [Virtual Reality Exposure Therapy] explode all trees

#104 psychological near/2 desensit*:ti,ab,kw (Word variations have been searched)

#105 “Eye Movement Desensitization Reprocessing”:ti,ab,kw or “Eye Movement Desensitisation Reprocessing”:ti,ab,kw (Word variations have been searched) #106 EMDR:ti,ab,kw (Word variations have been searched)

#107 exposure near/1 (therap* or treat*):ti,ab,kw (Word variations have been searched)

#108 “live exposure”:ti,ab,kw (Word variations have been searched)

#109 “imaginal exposure”:ti,ab,kw (Word variations have been searched)

#110 “prolonged exposure therapy”:ti,ab,kw (Word variations have been searched)

#111 “imaginal flooding”:ti,ab,kw (Word variations have been searched)

#112 “exposure inhibition therapy”:ti,ab,kw (Word variations have been searched) #113 “implosive therapy”:ti,ab,kw (Word variations have been searched)

#114 “image habituation”:ti,ab,kw (Word variations have been searched)

#115 “inoculation training”:ti,ab,kw (Word variations have been searched)

#116 MeSH descriptor: [Acceptance and Commitment Therapy] explode all trees

#117 acceptance near/2 therap*:ti,ab,kw (Word variations have been searched)

#118 commitment near/2 therap*:ti,ab,kw (Word variations have been searched)

#119 MeSH descriptor: [Hypnosis] explode all trees #120 hypnosis:ti,ab,kw (Word variations have been searched)

#121 hypnotherap*:ti,ab,kw (Word variations have been searched)

#122 MeSH descriptor: [Mindfulness] explode all trees

#123 mindfulness:ti,ab,kw (Word variations have been searched)

#124 supportive near/1 therap*:ti,ab,kw (Word variations have been searched)

#125 non-directive near/1 counsel*:ti,ab,kw (Word variations have been searched)

#126 nondirective near/2 counsel*:ti,ab,kw (Word variations have been searched) #127 “non directive” near/1 counsel*:ti,ab,kw (Word variations have been searched)

#128 MeSH descriptor: [Psychotherapy] explode all trees

#129 MeSH descriptor: [Psychotherapy, Brief] explode all trees

#130 MeSH descriptor: [Cognitive Therapy] explode all trees

#131 MeSH descriptor: [Psychotherapy, Group] explode all trees

#132 MeSH descriptor: [Psychotherapy, Multiple] explode all trees

#133 MeSH descriptor: [Psychotherapy, Psychodynamic] explode all trees #134 MeSH descriptor: [Psychotherapy, Rational-Emotive] explode all trees

#135 psychodynamic near/1 therap*:ti,ab,kw (Word variations have been searched)

#136 interpersonal near/1 psychotherap*:ti,ab,kw (Word variations have been searched)

#137 compassion near/2 therap*:ti,ab,kw (Word variations have been searched)

#138 “accelerated resolution”:ti,ab,kw (Word variations have been searched)

#139 sensorimotor near/2 therap*:ti,ab,kw (Word variations have been searched) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 127 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 16 Search strategy for CENTRAL via The Cochrane Library (continued)

#140 schema near/1 therap*:ti,ab,kw (Word variations have been searched) #141 MeSH descriptor: [Counseling] explode all trees

#142 #84 or #85 or #86 or #87 or #88 or #89 or #90 or #91 or #92 or #93 or #94 or #95 or #96 or #97 or #98 or #99 or #100 or #101 or #102 or #103 or #104 or #105 or #106 or #107 or #108 or #109 or #110 or #111 or #112 or #113 or #114 or #115 or #116 or #117 or #118 or #119 or #120 or #121 or #122 or #123 or #124 or #125 or #126 or #127 or #128 or #129 or #130 or #131 or #132 or #133 or #134 or #135 or #136 or #137 or #138 or #139 or #140 or #141

#143 MeSH descriptor: [Hypnotics and Sedatives] explode all trees

#144 MeSH descriptor: [Alprazolam] explode all trees #145 MeSH descriptor: [Amobarbital] explode all trees

#146 MeSH descriptor: [Azaperone] explode all trees

#147 MeSH descriptor: [Barbital] explode all trees

#148 MeSH descriptor: [Bromisovalum] explode all trees

#149 MeSH descriptor: [Chloral Hydrate] explode all trees

#150 MeSH descriptor: [Chloralose] explode all trees

#151 MeSH descriptor: [Chlordiazepoxide] explode all trees #152 MeSH descriptor: [Chlormethiazole] explode all trees

#153 MeSH descriptor: [Dexmedetomidine] explode all trees

#154 MeSH descriptor: [Diazepam] explode all trees

#155 MeSH descriptor: [Diphenhydramine] explode all trees

#156 MeSH descriptor: [Eszopiclone] explode all trees

#157 MeSH descriptor: [Ethchlorvynol] explode all trees

#158 MeSH descriptor: [Etomidate] explode all trees #159 MeSH descriptor: [Etorphine] explode all trees

#160 MeSH descriptor: [Flurazepam] explode all trees

#161 MeSH descriptor: [Glutethimide] explode all trees

#162 MeSH descriptor: [Hexobarbital] explode all trees

#163 MeSH descriptor: [Lorazepam] explode all trees

#164 MeSH descriptor: [Medazepam] explode all trees

#165 MeSH descriptor: [Medetomidine] explode all trees

#166 MeSH descriptor: [Mephobarbital] explode all trees #167 MeSH descriptor: [Meprobamate] explode all trees

#168 MeSH descriptor: [Methapyrilene] explode all trees

#169 MeSH descriptor: [Methaqualone] explode all trees

#170 MeSH descriptor: [Midazolam] explode all trees

#171 MeSH descriptor: [Nitrazepam] explode all trees

#172 MeSH descriptor: [Oxazepam] explode all trees

#173 MeSH descriptor: [Paraldehyde] explode all trees #174 MeSH descriptor: [Pentobarbital] explode all trees

#175 MeSH descriptor: [Phenobarbital] explode all trees

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TABLE 16 Search strategy for CENTRAL via The Cochrane Library (continued)

#176 MeSH descriptor: [Propofol] explode all trees #177 MeSH descriptor: [Secobarbital] explode all trees

#178 MeSH descriptor: [Temazepam] explode all trees

#179 MeSH descriptor: [Thiamylal] explode all trees

#180 MeSH descriptor: [Thiopental] explode all trees

#181 MeSH descriptor: [Xylazine] explode all trees

#182 #143 or #144 or #145 or #146 or #147 or #148 or #149 or #150 or #151 or #152 or #153 or #154 or #155 or #156 or #157 or #158 or #159 or #160 or #161 or #162 or #163 or #164 or #165 or #166 or #167 or #168 or #169 or #170 or #171 or #172 or #173 or #174 or #175 or #176 or #177 or #178 or #179 or #180 or #181 #183 “z drugs”:ti,ab,kw (Word variations have been searched)

#184 MeSH descriptor: [Anti-Anxiety Agents] explode all trees

#185 MeSH descriptor: [Bromazepam] explode all trees

#186 MeSH descriptor: [Buspirone] explode all trees

#187 MeSH descriptor: [Chlormezanone] explode all trees

#188 MeSH descriptor: [Estazolam] explode all trees

#189 MeSH descriptor: [Flunitrazepam] explode all trees #190 MeSH descriptor: [Fluvoxamine] explode all trees

#191 MeSH descriptor: [Nordazepam] explode all trees

#192 MeSH descriptor: [Ondansetron] explode all trees

#193 MeSH descriptor: [Oxprenolol] explode all trees

#194 MeSH descriptor: [Prazepam] explode all trees

#195 MeSH descriptor: [Pregabalin] explode all trees

#196 MeSH descriptor: [Ritanserin] explode all trees #197 MeSH descriptor: [Tranylcypromine] explode all trees

#198 MeSH descriptor: [Trazodone] explode all trees

#199 MeSH descriptor: [Triazolam] explode all trees

#200 MeSH descriptor: [Zolazepam] explode all trees

#201 MeSH descriptor: [Benzodiazepines] explode all trees

#202 MeSH descriptor: [Benzodiazepinones] explode all trees

#203 sedative near/1 antihistamine*:ti,ab,kw (Word variations have been searched) #204 MeSH descriptor: [Promethazine] explode all trees

#205 #183 or #184 or #185 or #186 or #187 or #188 or #189 or #190 or #191 or #192 or #193 or #194 or #195 or #196 or #197 or #198 or #199 or #200 or #201 or #202 or #203 or #204

#206 MeSH descriptor: [Antidepressive Agents] explode all trees #207 MeSH descriptor: [Benactyzine] explode all trees

#208 MeSH descriptor: [Clorgyline] explode all trees

#209 MeSH descriptor: [Deanol] explode all trees

#210 MeSH descriptor: [Desvenlafaxine Succinate] explode all trees

#211 MeSH descriptor: [Duloxetine Hydrochloride] explode all trees continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 129 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 16 Search strategy for CENTRAL via The Cochrane Library (continued)

#212 MeSH descriptor: [Iproniazid] explode all trees #213 MeSH descriptor: [Isocarboxazid] explode all trees

#214 MeSH descriptor: [Lithium Compounds] explode all trees

#215 MeSH descriptor: [Moclobemide] explode all trees

#216 MeSH descriptor: [Nialamide] explode all trees

#217 MeSH descriptor: [Phenelzine] explode all trees

#218 MeSH descriptor: [Pizotyline] explode all trees

#219 MeSH descriptor: [Rolipram] explode all trees #220 MeSH descriptor: [Sertraline] explode all trees

#221 MeSH descriptor: [Tranylcypromine] explode all trees

#222 MeSH descriptor: [Vilazodone Hydrochloride] explode all trees

#223 MeSH descriptor: [Imipramine] explode all trees

#224 #206 or #207 or #208 or #209 or #210 or #211 or #212 or #213 or #214 or #215 or #216 or #217 or #218 or #219 or #220 or #221 or #222 or #223

#225 MeSH descriptor: [Antipsychotic Agents] explode all trees

#226 MeSH descriptor: [Acepromazine] explode all trees

#227 MeSH descriptor: [Aripiprazole] explode all trees

#228 MeSH descriptor: [Azaperone] explode all trees

#229 MeSH descriptor: [Benperidol] explode all trees #230 MeSH descriptor: [Butaclamol] explode all trees

#231 MeSH descriptor: [Chlorpromazine] explode all trees

#232 MeSH descriptor: [Chlorprothixene] explode all trees

#233 MeSH descriptor: [Clopenthixol] explode all trees

#234 MeSH descriptor: [Clozapine] explode all trees

#235 MeSH descriptor: [Droperidol] explode all trees

#236 MeSH descriptor: [Etazolate] explode all trees #237 MeSH descriptor: [Flupenthixol] explode all trees

#238 MeSH descriptor: [Fluphenazine] explode all trees

#239 MeSH descriptor: [Fluspirilene] explode all trees

#240 MeSH descriptor: [Haloperidol] explode all trees

#241 MeSH descriptor: [Loxapine] explode all trees

#242 MeSH descriptor: [Mesoridazine] explode all trees

#243 MeSH descriptor: [Methiothepin] explode all trees #244 MeSH descriptor: [Methotrimeprazine] explode all trees

#245 MeSH descriptor: [Molindone] explode all trees

#246 MeSH descriptor: [Paliperidone Palmitate] explode all trees

#247 MeSH descriptor: [Penfluridol] explode all trees

#248 MeSH descriptor: [Perazine] explode all trees

#249 MeSH descriptor: [Perphenazine] explode all trees

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TABLE 16 Search strategy for CENTRAL via The Cochrane Library (continued)

#250 MeSH descriptor: [Pimozide] explode all trees #251 MeSH descriptor: [Prochlorperazine] explode all trees

#252 MeSH descriptor: [Promazine] explode all trees

#253 MeSH descriptor: [Quetiapine Fumarate] explode all trees

#254 MeSH descriptor: [Raclopride] explode all trees

#255 MeSH descriptor: [Remoxipride] explode all trees

#256 MeSH descriptor: [Reserpine] explode all trees

#257 MeSH descriptor: [Risperidone] explode all trees #258 MeSH descriptor: [Ritanserin] explode all trees

#259 MeSH descriptor: [Spiperone] explode all trees

#260 MeSH descriptor: [Sulpiride] explode all trees

#261 MeSH descriptor: [Thioridazine] explode all trees

#262 MeSH descriptor: [Thiothixene] explode all trees

#263 MeSH descriptor: [Tiapride Hydrochloride] explode all trees

#264 MeSH descriptor: [Trifluoperazine] explode all trees #265 MeSH descriptor: [Trifluperidol] explode all trees

#266 MeSH descriptor: [Triflupromazine] explode all trees

#267 “olanzapine”:ti,ab,kw (Word variations have been searched)

#268 #225 or #226 or #227 or #228 or #229 or #230 or #231 or #232 or #233 or #234 or #235 or #236 or #237 or #238 or #239 or #240 or #241 or #242 or #243 or #244 or #245 or #246 or #247 or #248 or #249 or #250 or #251 or #252 or #253 or #254 or #255 or #256 or #257 or #258 or #259 or #260 or #261 or #262 or #263 or #264 or #265 or #266 or #267

#269 MeSH descriptor: [Anticonvulsants] explode all trees

#270 MeSH descriptor: [Acetazolamide] explode all trees

#271 MeSH descriptor: [Bromides] explode all trees

#272 MeSH descriptor: [Carbamazepine] explode all trees

#273 MeSH descriptor: [Clonazepam] explode all trees #274 MeSH descriptor: [Clorazepate Dipotassium] explode all trees

#275 MeSH descriptor: [Diazepam] explode all trees

#276 MeSH descriptor: [Dimethadione] explode all trees

#277 MeSH descriptor: [Estazolam] explode all trees

#278 MeSH descriptor: [Ethosuximide] explode all trees

#279 MeSH descriptor: [Flunarizine] explode all trees

#280 MeSH descriptor: [Lorazepam] explode all trees #281 MeSH descriptor: [Magnesium Sulfate] explode all trees

#282 MeSH descriptor: [Medazepam] explode all trees

#283 MeSH descriptor: [Mephenytoin] explode all trees

#284 MeSH descriptor: [Mephobarbital] explode all trees

#285 MeSH descriptor: [Meprobamate] explode all trees continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 131 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 16 Search strategy for CENTRAL via The Cochrane Library (continued)

#286 MeSH descriptor: [Nitrazepam] explode all trees #287 MeSH descriptor: [Paraldehyde] explode all trees

#288 MeSH descriptor: [Phenobarbital] explode all trees

#289 MeSH descriptor: [Phenytoin] explode all trees

#290 MeSH descriptor: [Pregabalin] explode all trees

#291 MeSH descriptor: [Primidone] explode all trees

#292 MeSH descriptor: [Riluzole] explode all trees

#293 MeSH descriptor: [Thiopental] explode all trees #294 MeSH descriptor: [Tiletamine] explode all trees

#295 MeSH descriptor: [Trimethadione] explode all trees

#296 MeSH descriptor: [Valproic Acid] explode all trees

#297 MeSH descriptor: [Vigabatrin] explode all trees

#298 #269 or #270 or #271 or #272 or #273 or #274 or #275 or #276 or #277 or #278 or #279 or #280 or #281 or #282 or #283 or #284 or #285 or #286 or #287 or #288 or #289 or #290 or #291 or #292 or #293 or #294 or #295 or #296 or #297

#299 MeSH descriptor: [Antimanic Agents] explode all trees #300 MeSH descriptor: [Lithium Chloride] explode all trees

#301 “lamotrigine”:ti,ab,kw (Word variations have been searched)

#302 “topiramate”:ti,ab,kw (Word variations have been searched)

#303 MeSH descriptor: [Monoamine Oxidase Inhibitors] explode all trees

#304 MeSH descriptor: [Chlorpheniramine] explode all trees

#305 MeSH descriptor: [Clorgyline] explode all trees

#306 MeSH descriptor: [Cuprizone] explode all trees #307 MeSH descriptor: [Furazolidone] explode all trees

#308 MeSH descriptor: [Harmaline] explode all trees

#309 MeSH descriptor: [Harmine] explode all trees

#310 MeSH descriptor: [Isocarboxazid] explode all trees

#311 MeSH descriptor: [Moclobemide] explode all trees

#312 MeSH descriptor: [Monocrotophos] explode all trees

#313 MeSH descriptor: [Pargyline] explode all trees #314 MeSH descriptor: [Selegiline] explode all trees

#315 MeSH descriptor: [Tranylcypromine] explode all trees

#316 MeSH descriptor: [Prazosin] explode all trees

#317 MeSH descriptor: [N-Methyl-3,4-methylenedioxyamphetamine] explode all trees

#318 MDMA:ti,ab,kw or ecstasy:kw (Word variations have been searched)

#319 #299 or #300 or #301 or #302 or #303 or #304 or #305 or #306 or #307 or #308 or #309 or #310 or #311 or #312 or #313 or #314 or #315 or #316 or #317 or #318

#320 #182 or #205 or #224 or #268 or #298 or #319

#321 #83 and #142

#322 #83 and #320

#323 #321 or #322

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EMBASE via Ovid

Search date: 19 April 2017.

Records retrieved: 5473.

Date range searched: 1974 to 2017 week 16.

TABLE 17 Search strategy for EMBASE via Ovid

1 exp Violence/ (127,415) 2 violence.ti,ab. (42,364) 3 Exposure to Violence/ (299) 4 Domestic Violence/(8799) 5 Sexual Violence/ (1468) 6 Battered Woman/ (3115) 7 (batter$ adj2 (wife$ or wive$ or woman or women or men or husband$ or partner$)).ti,ab. (973) 8 (physical$ adj2 (abus$ or assault$ or violen$ or aggress$)).ti,ab. (12,350) 9 (emotional$ adj2 abus$).ti,ab. (2304) 10 Rape/(7255) 11 Sexual Assault/ (1440) 12 rape.ti,ab. (7034) 13 (sexual$ adj2 (abus$ or assault$ or violen$ or aggress$)).ti,ab. (23,249) 14 Child Sexual Abuse/ (8661) 15 child$ sexual abuse.ti,ab. (4983) 16 Child Abuse/ (27,390) 17 (child$ adj2 exploit$).ti,ab. (221) 18 child neglect.ti,ab. (490) 19 (child$ adj2 trauma).ti,ab. (6375) 20 (non accidental injur$ or non-accidental injur$ or nonaccidental injury).ti,ab. (755) 21 Human Rights Abuse/ (1442) 22 Human Trafficking/(259) 23 ((human or person or people) adj2 (traffick$ or exploit$)).ti,ab. (907) 24 ((forced or exploit$) adj2 labour).ti,ab. (62) 25 Organ Trafficking/ (190) 26 Slavery/ (115) 27 Torture/ (2635) 28 (slavery or enslave$ or torture$).ti,ab. (2768) 29 Prostitution/ (8919) 30 (prostitut$ or brothel$).ti,ab. (3430) 31 (sex$ adj2 (exploit$ or traffick$)).ti,ab. (618) 32 exp Terrorism/ (9017) 33 (terrorism or terrorist$).ti,ab. (6169) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 133 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 17 Search strategy for EMBASE via Ovid (continued)

34 political terror$.ti,ab. (19) 35 Torture/ (2635) 36 exp warfare/ (18,460) 37 War crime/ (174) 38 Genocide/ (334) 39 Holocaust/ (369) 40 Ethnic Conflict/ (58) 41 (civil adj (unrest or conflict$ or disturbance$ or war or wars or warfare)).ti,ab. (1866) 42 (persecution or victimization or victimisation).ti,ab. (7768) 43 (captivity or imprison$ or concentration camp$).ti,ab. (6611) 44 exp Disasters/ (27,191) 45 natural disaster$.ti,ab. (3220) 46 (earthquake$ or tsunami$).ti,ab. (8306) 47 (humanitarian adj (crisis or crises)).ti,ab. (230) 48 (catastrophe$ or catastrophic event$ or catastrophic experience$).ti,ab. (7315) 49 exp Survivor/ (65,046) 50 Refugee/ (9945) 51 (asylum seeker$ or refugee$ or migrant$).ti,ab. (22,105) 52 ((forcibly or internally) adj2 displace$).ti,ab. (518) 53 (displace$ adj2 (people or person$ or civilian$)).ti,ab. (769) 54 Crime Victim/(1526) 55 exp Childhood Trauma Survivor/ (209) 56 Disaster Victim/ (296) 57 exp Prisoner/ (15,304) 58 Prisoner of War/ (396) 59 Slave/ (82) 60 Veteran/ (24,063) 61 Soldier/ (29,325) 62 ((expose$ or exposure) adj2 (abuse or assault$ or disaster$ or terror$ or torture$ or trauma$ or rape or violen$ or war or warfare)).ti,ab. (8060) 63 (survivor$ adj2 (abuse or assault$ or disaster$ or terror$ or torture$ or trauma$ or rape or violen$ or war or warfare)).ti,ab. (2541) 64 (victim$ adj2 (abuse or assault$ or crime or disaster$ or rape or terror$ or torture$ or trauma$ or violen$ or war or warfare)).ti,ab. (9275) 65 (witness$ adj2 (abuse or assault$ or disaster$ or rape or terror$ or torture$ or trauma$ or violen$ or war or warfare)).ti,ab. (1147) 66 1or2or3or4or5or6or7or8or9or10or11or12or13or14or15or16or17or18or19or20or21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 or 62 or 63 or 64 or 65 (372,799) 67 Posttraumatic Stress Disorder/ (48,288) 68 (PTSD or CPTSD).ti,ab. (22,853) 69 posttrauma$.ti,ab. (35,543) 70 post-trauma$.ti,ab. (32,384)

134

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TABLE 17 Search strategy for EMBASE via Ovid (continued)

71 “post trauma$”.ti,ab. (32,384) 72 post traumatic stress.ti,ab. (12,118) 73 post traumatic stress.kw. (2904) 74 combat stress$.ti,ab. (414) 75 combat disorder$.ti,ab. (19) 76 DESNOS.ti,ab. (37) 77 “Disorders of Extreme Distress Not Otherwise Specified”.ti,ab. (0) 78 complex trauma$.ti,ab. (468) 79 (complex adj3 trauma$).ti,ab. (1446) 80 traumatic stress.ti,ab. (14,496) 81 traumatic memor$.ti,ab. (767) 82 traumatization.ti,ab. (1253) 83 traumatisation.ti,ab. (258) 84 (trauma$ adj3 (expos$ or event$ or experienc$)).ti,ab. (20,684) 85 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 or 75 or 76 or 77 or 78 or 79 or 80 or 81 or 82 or 83 or 84 (99,034) 86 66 and 85 (29,961) 87 exp Cognitive Therapy/ (44,498) 88 cognitive behaviour$ therapy.ti,ab. (5617) 89 cognitive behavior$ therapy.ti,ab. (10,869) 90 cognitive restructuring.ti,ab. (1117) 91 cognitive rescripting.ti,ab. (0) 92 cognitive processing therapy.ti,ab. (197) 93 CPT.ti,ab. (15,303) 94 cognitive therapy.ti,ab. (3567) 95 cognitive behavioural treatment$.ti,ab. (569) 96 cognitive behavioral treatment$.ti,ab. (1915) 97 (CBT or TFCBT).ti,ab. (11,649) 98 cognitive trauma therapy.ti,ab. (7) 99 trauma focus$ CBT.ti,ab. (48) 100 87 or 88 or 89 or 90 or 91 or 92 or 93 or 94 or 95 or 96 or 97 or 98 or 99 (65,898) 101 exp Behavior Therapy/ (42,878) 102 (behavior$ adj2 (therap$ or treat$ or modif$)).ti,ab. (35,788) 103 (behaviour$ adj2 (therap$ or treat$ or modif$)).ti,ab. (13,871) 104 (dialectical behavio$ adj (therap$ or treat$)).ti,ab. (829) 105 biofeedback, psychology/or feedback, sensory/or neurofeedback/ (21,789) 106 (biofeedback or neurofeedback or sensory feedback).ti,ab. (11,442) 107 eye movement desensitization reprocessing/or implosive therapy/or virtual reality exposure therapy/ (414) 108 (psychological adj2 desensiti$).ti,ab. (9) 109 eye movement desensiti?ation reprocessing.ti,ab. (39) 110 EMDR.ti,ab. (560) 111 (exposure adj (therap$ or treat$)).ti,ab. (2851) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 135 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 17 Search strategy for EMBASE via Ovid (continued)

112 live exposure.ti,ab. (16) 113 imaginal exposure.ti,ab. (183) 114 prolonged exposure therapy.ti,ab. (120) 115 imaginal flooding.ti,ab. (27) 116 exposure inhibition therap$.ti,ab. (0) 117 implosive therap$.ti,ab. (58) 118 image habituation.ti,ab. (4) 119 inoculation training.ti,ab. (114) 120 101 or 102 or 103 or 104 or 105 or 106 or 107 or 108 or 109 or 110 or 111 or 112 or 113 or 114 or 115 or 116 or 117 or 118 or 119 (107,793) 121 “Acceptance and Commitment Therapy”/ (780) 122 (acceptance adj2 therap$).ti,ab. (384) 123 (commitment adj2 therap$).ti,ab. (858) 124 Hypnosis/ (14,590) 125 (hypnosis or hypnotherap$).ti,ab. (9008) 126 Mindfulness/ (3696) 127 mindfulness.ti,ab. (5250) 128 supportive therap$.ti,ab. (5535) 129 (non-directive adj (counselling or counseling)).ti,ab. (118) 130 (nondirective adj (counselling or counseling)).ti,ab. (51) 131 (non directive adj (counselling or counseling)).ti,ab. (118) 132 Psychotherapy/or Group Therapy/or Psychodynamic Psychotherapy/ (104,777) 133 psychodynamic therap$.ti,ab. (636) 134 inter personal psychotherap$.ti,ab. (1) 135 interpersonal psychotherap$.ti,ab. (940) 136 IPT.ti,ab. (2383) 137 (compassion adj2 therap$).ti,ab. (58) 138 accelerated resolution.ti,ab. (120) 139 sensorimotor therap$.ti,ab. (24) 140 schema therapy.ti,ab. (180) 141 (stress adj2 manag$).ti,ab. (6629) 142 supportive therap$.ti,ab. (5535) 143 Counseling/ (75,492) 144 (non-directive counsel$ or non directive counsel$ or nondirective counsel$).ti,ab. (170) 145 compassion therap$.ti,ab. (2) 146 121 or 122 or 123 or 124 or 125 or 126 or 127 or 128 or 129 or 130 or 131 or 132 or 133 or 134 or 135 or 136 or 137 or 138 or 139 or 140 or 141 or 142 or 143 or 144 or 145 (209,736) 147 100 or 120 or 146 (330,152) 148 hypnotic sedative agent/or alprazolam/or amobarbital/or azaperone/or barbital/or bromisovalum/or chloral hydrate/or chloralose/or chlordiazepoxide/or chlomethiazole/or dexmedetomidine/or diazepam/or diphenhydramine/or eszopiclone/or ethchlorvynol/or etomidate/or etorphine/or flurazepam/or glutethimide/or hexobarbital/or lorazepam/ or medazepam/or medetomidine/or methylphenobarbital/or meprobamate/or methapyrilene/or methaqualone/or midazolam/or nitrazepam/or oxazepam/or paraldehyde/or pentobarbital/or phenobarbital/or propofol/or secobarbital/ or temazepam/or thiamylal/or thiopental/or xylazine/ (321,753)

136

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TABLE 17 Search strategy for EMBASE via Ovid (continued)

149 z drugs.ti,ab. (207) 150 anxiolytic agent/or bromazepam/or buspirone/or chlormezanone/or clorazepate dipotassium/or estazolam/or flunitrazepam/or fluvoxamine/or nordazepam/or ondansetron/or oxprenolol/or prazepam/or pregabalin/or ritanserin/or tranylcypromine/or trazodone/or triazolam/or zolazepam/ (100,358) 151 benzodiazepine derivative/ (40,227) 152 sedative antihistamine$.ti,ab. (114) 153 promethazine/ (13,661) 154 antidepressive agent/or benactyzine/or clorgyline/or deanol/or desvenlafaxine/or duloxetine/or iproniazid/or isocarboxazid/or lithium carbonate/or lithium derivative/or moclobemide/or nialamide/or phenelzine/or pizotifen/or rolipram/or sertraline/or tranylcypromine/or vilazodone/ (147,901) 155 Imipramine/ (34,101) 156 mirtazapine/ (10,903) 157 neuroleptic agent/or acepromazine/or aripiprazole/or azaperone/or benperidol/or butaclamol/or chlorpromazine/ or chlorprothixene/or clopenthixol/or clozapine/or droperidol/or etazolate/or flupentixol/or fluphenazine/or fluspirilene/ or haloperidol/or loxapine/or lurasidone/or mesoridazine/or metitepine/or methotrimeprazine/or molindone/or ondansetron/or paliperidone/or penfluridol/or perazine/or perphenazine/or pimozide/or prochlorperazine/or promazine/ or quetiapine/or raclopride/or remoxipride/or reserpine/or risperidone/or ritanserin/or spiperone/or sulpiride/or thioridazine/or tiothixene/or tiapride/or trifluoperazine/or trifluperidol/or triflupromazine/ (250,352) 158 olanzapine/ (30,419) 159 anticonvulsive agent/or acetazolamide/or bromides/or carbamazepine/or clonazepam/or clorazepate dipotassium/ or diazepam/or dimethadione/or estazolam/or ethosuximide/or flunarizine/or lorazepam/or magnesium sulfate/or medazepam/or mephenytoin/or methylphenobarbital/or meprobamate/or nitrazepam/or paraldehyde/or phenobarbital/ or phenytoin/or pregabalin/or primidone/or riluzole/or thiopental/or tiletamine/or trimethadione/or valproic acid/or vigabatrin/ (370,923) 160 tranquilizer/or lithium chloride/or lithium derivative/ (25,358) 161 lamotrigine/ (21,972) 162 topiramate/ (18,900) 163 monoamine oxidase inhibitor/or chlorphenamidine/or clorgyline/or cuprizone/or furazolidone/or harmaline/or harmine/or isocarboxazid/or moclobemide/or monocrotophos/or pargyline/or selegiline/or tranylcypromine/ (44,538) 164 Prazosin/ (22,822) 165 3,4 methylenedioxyamphetamine/ (2221) 166 (MDMA or ecstasy).ti,ab. (6467) 167 148 or 149 or 150 or 151 or 152 or 153 or 154 or 155 or 156 or 157 or 158 or 159 or 160 or 161 or 162 or 163 or 164 or 165 or 166 (904,230) 168 86 and 147 (4620) 169 86 and 167 (1616) 170 168 or 169 (5607) 171 limit 170 to yr=“1992 -Current” (5473)

International Pharmaceutical Abstracts via ProQuest

Search date: 30 August 2017.

The initial search identified 625 records.

Date range searched: 1970 onwards.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 137 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 18 Search strategy for International Pharmaceutical Abstracts via ProQuest

(SU.EXACT(“Stress disorders”)) OR (PTSD or CPTSD) OR (posttrauma* or post-trauma*) OR (“post traumatic stress”)OR (“combat disorder*”)OR(“combat stress”) OR DESNOS OR (traumatisation OR traumatization) OR (complex NEAR/3 trauma*) OR (trauma* NEAR/3 (expos* or event* or experienc*))

MEDLINE via Ovid

Search date: 18 April 2017.

Records retrieved: 2818.

Database: Ovid MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE.

Date range searched: 1946 to present.

TABLE 19 Search strategy for MEDLINE via Ovid

1 exp Violence/ (84,653)

2 violence.ti,ab. (38,287)

3 Domestic Violence/ (5769)

4 Intimate Partner Violence/ (716)

5 Battered Women/ (2579)

6 (batter$ adj2 (wife$ or wive$ or woman or women or men or husband$ or partner$)).ti,ab. (870)

7 (physical$ adj2 (abus$ or assault$ or violen$ or aggress$)).ti,ab. (10,464)

8 (emotional$ adj2 abus$).ti,ab. (1749) 9 Rape/ (6157)

10 rape.ti,ab. (6600)

11 (sexual$ adj2 (abus$ or assault$ or violen$ or aggress$)).ti,ab. (19,466)

12 Child Sexual Abuse/ (9551)

13 child$ sexual abuse.ti,ab. (4339)

14 (child$ adj2 exploit$).ti,ab. (200)

15 child neglect.ti,ab. (468) 16 (child$ adj2 trauma).ti,ab. (4689)

17 (non accidental injur$ or non-accidental injur$ or nonaccidental injury).ti,ab. (533)

18 Human Rights Abuses/ (734)

19 Human Trafficking/ (177)

20 ((human or person or people) adj2 (traffick$ or exploit$)).ti,ab. (818)

21 ((forced or exploit$) adj2 labour).ti,ab. (56)

22 Organ Trafficking/ (33) 23 Slavery/ (45)

24 Torture/ (1996)

138

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TABLE 19 Search strategy for MEDLINE via Ovid (continued)

25 (slavery or enslave$ or torture$).ti,ab. (2480) 26 Sex Work/ (5675)

27 (prostitut$ or brothel$).ti,ab. (3946)

28 (sex$ adj2 (exploit$ or traffick$)).ti,ab. (561)

29 Terrorism/ (4718)

30 (terrorism or terrorist$).ti,ab. (5408)

31 political terror$.ti,ab. (16)

32 Torture/ (1996) 33 exp warfare/ (35,511)

34 exp Armed Conflicts/ (8467)

35 War crimes/ (1197)

36 Genocide/ (84)

37 Holocaust/ (782)

38 Ethnic Cleansing/ (0)

39 (civil adj (unrest or conflict$ or disturbance$ or war or wars or warfare)).ti,ab. (1859) 40 (persecution or victimization or victimisation).ti,ab. (7276)

41 (captivity or imprison$ or concentration camp$).ti,ab. (6151)

42 exp Disasters/ (67,463)

43 Earthquakes/ (3095)

44 Tsunamis/ (708)

45 natural disaster$.ti,ab. (2928)

46 (earthquake$ or tsunami$).ti,ab. (7947)

47 (humanitarian adj (crisis or crises)).ti,ab. (221) 48 (catastrophe$ or catastrophic event$ or catastrophic experience$).ti,ab. (5922)

49 exp Survivors/ (22,782)

50 Refugees/ (8204)

51 (asylum seeker$ or refugee$ or migrant$).ti,ab. (21,535)

52 ((forcibly or internally) adj2 displace$).ti,ab. (476)

53 (displace$ adj2 (people or person$ or civilian$)).ti,ab. (763)

54 Crime Victims/ (7200) 55 Adult Survivors of Child Abuse/ (1437)

56 Disaster Victims/ (96)

57 Prisoners/ (15,110)

58 Prisoners of War/ (469)

59 Slaves/ (31)

60 Veterans/ (13,136)

61 Military Personnel/ (35,416) 62 ((expose$ or exposure) adj2 (abuse or assault$ or disaster$ or terror$ or torture$ or trauma$ or rape or violen$ or war or warfare)).ti,ab. (7019) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 139 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 19 Search strategy for MEDLINE via Ovid (continued)

63 (survivor$ adj2 (abuse or assault$ or disaster$ or terror$ or torture$ or trauma$ or rape or violen$ or war or warfare)).ti,ab. (2319)

64 (victim$ adj2 (abuse or assault$ or crime or disaster$ or rape or terror$ or torture$ or trauma$ or violen$ or war or warfare)).ti,ab. (8160)

65 (witness$ adj2 (abuse or assault$ or disaster$ or rape or terror$ or torture$ or trauma$ or violen$ or war or warfare)).ti,ab. (1041)

66 1or2or3or4or5or6or7or8or9or10or11or12or13or14or15or16or17or18or19or20or21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 or 62 or 63 or 64 or 65 (331,505) 67 Stress Disorders, Post Traumatic/ (26,733)

68 (PTSD or CPTSD).ti,ab. (18,107)

69 posttrauma$.ti,ab. (30,066)

70 post-trauma$.ti,ab. (25,637)

71 “post trauma$”.ti,ab. (25,637)

72 post traumatic stress.ti,ab. (9289)

73 post traumatic stress.kw. (88) 74 combat stress$.ti,ab. (343)

75 combat disorder$.ti,ab. (15)

76 DESNOS.ti,ab. (31)

77 “Disorders of Extreme Distress Not Otherwise Specified”.ti,ab. (0)

78 complex trauma$.ti,ab. (403)

79 (complex adj3 trauma$).ti,ab. (1217)

80 traumatic stress.ti,ab. (10,740) 81 traumatic memor$.ti,ab. (579)

82 traumatization.ti,ab. (990)

83 traumatisation.ti,ab. (192)

84 (trauma$ adj3 (expos$ or event$ or experienc$)).ti,ab. (16,288)

85 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 or 75 or 76 or 77 or 78 or 79 or 80 or 81 or 82 or 83 or 84 (75,076)

86 66 and 85 (24,059)

87 exp Cognitive Therapy/ (22,441) 88 cognitive behaviour$ therapy.ti,ab. (3982)

89 cognitive behavior$ therapy.ti,ab. (8052)

90 cognitive restructuring.ti,ab. (723)

91 cognitive rescripting.ti,ab. (0)

92 cognitive processing therapy.ti,ab. (178)

93 CPT.ti,ab. (10,770)

94 cognitive therapy.ti,ab. (2397) 95 cognitive behavioural treatment$.ti,ab. (403)

96 cognitive behavioral treatment$.ti,ab. (1378)

97 (CBT or TFCBT).ti,ab. (7996)

140

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TABLE 19 Search strategy for MEDLINE via Ovid (continued)

98 cognitive trauma therapy.ti,ab. (6) 99 trauma focus$ CBT.ti,ab. (31)

100 87 or 88 or 89 or 90 or 91 or 92 or 93 or 94 or 95 or 96 or 97 or 98 or 99 (40,659)

101 exp Behavior Therapy/ (64,582)

102 (behavior$ adj2 (therap$ or treat$ or modif$)).ti,ab. (26,789)

103 (behaviour$ adj2 (therap$ or treat$ or modif$)).ti,ab. (9862)

104 (dialectical behavio$ adj (therap$ or treat$)).ti,ab. (581)

105 biofeedback, psychology/or feedback, sensory/or neurofeedback/ (9330) 106 (biofeedback or neurofeedback or sensory feedback).ti,ab. (8461)

107 eye movement desensitization reprocessing/or implosive therapy/or virtual reality exposure therapy/ (1347)

108 (psychological adj2 desensiti$).ti,ab. (4)

109 eye movement desensiti?ation reprocessing.ti,ab. (25)

110 EMDR.ti,ab. (372)

111 (exposure adj (therap$ or treat$)).ti,ab. (2282)

112 live exposure.ti,ab. (11) 113 imaginal exposure.ti,ab. (147)

114 prolonged exposure therapy.ti,ab. (99)

115 imaginal flooding.ti,ab. (13)

116 exposure inhibition therap$.ti,ab. (0)

117 implosive therap$.ti,ab. (43)

118 image habituation.ti,ab. (3)

119 inoculation training.ti,ab. (78)

120 101 or 102 or 103 or 104 or 105 or 106 or 107 or 108 or 109 or 110 or 111 or 112 or 113 or 114 or 115 or 116 or 117 or 118 or 119 (90,057)

121 “Acceptance and Commitment Therapy”/ (184)

122 (acceptance adj2 therap$).ti,ab. (257) 123 (commitment adj2 therap$).ti,ab. (603)

124 Hypnosis/ (8730)

125 (hypnosis or hypnotherap$).ti,ab. (7561)

126 Mindfulness/ (1325)

127 mindfulness.ti,ab. (4005)

128 supportive therap$.ti,ab. (3906)

129 (non-directive adj (counselling or counseling)).ti,ab. (100) 130 (nondirective adj (counselling or counseling)).ti,ab. (54)

131 (non directive adj (counselling or counseling)).ti,ab. (100)

132 Psychotherapy/or Psychotherapy, Brief/or Psychotherapy, Group/or Psychotherapy, Multiple/or Psychotherapy, Psychodynamic/or Psychotherapy, Rational-emotive/ (65,822) 133 psychodynamic therap$.ti,ab. (431)

134 inter personal psychotherap$.ti,ab. (1) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 141 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 19 Search strategy for MEDLINE via Ovid (continued)

135 interpersonal psychotherap$.ti,ab. (778) 136 IPT.ti,ab. (1907)

137 (compassion adj2 therap$).ti,ab. (39)

138 accelerated resolution.ti,ab. (86)

139 sensorimotor therap$.ti,ab. (21)

140 schema therapy.ti,ab. (106)

141 (stress adj2 manag$).ti,ab. (5168)

142 supportive therap$.ti,ab. (3906) 143 Counseling/(32,854)

144 (non-directive counsel$ or non directive counsel$ or nondirective counsel$).ti,ab. (155)

145 compassion therap$.ti,ab. (1)

146 121 or 122 or 123 or 124 or 125 or 126 or 127 or 128 or 129 or 130 or 131 or 132 or 133 or 134 or 135 or 136 or 137 or 138 or 139 or 140 or 141 or 142 or 143 or 144 or 145 (122,017)

147 100 or 120 or 146 (211,031)

148 “hypnotics and sedatives”/or alprazolam/or amobarbital/or azaperone/or barbital/or bromisovalum/or chloral hydrate/or chloralose/or chlordiazepoxide/or chlormethiazole/or dexmedetomidine/or diazepam/or diphenhydramine/ or eszopiclone/or ethchlorvynol/or etomidate/or etorphine/or flurazepam/or glutethimide/or hexobarbital/or lorazepam/or medazepam/or medetomidine/or mephobarbital/or meprobamate/or methapyrilene/or methaqualone/or midazolam/or nitrazepam/or oxazepam/or paraldehyde/or pentobarbital/or phenobarbital/or propofol/or secobarbital/ or temazepam/or thiamylal/or thiopental/or xylazine/ (114,648)

149 z drugs.ti,ab. (120)

150 anti-anxiety agents/or bromazepam/or buspirone/or chlormezanone/or clorazepate dipotassium/or estazolam/or flunitrazepam/or fluvoxamine/or nordazepam/or ondansetron/or oxprenolol/or prazepam/or pregabalin/or ritanserin/or tranylcypromine/or trazodone/or triazolam/or zolazepam/ (33,101) 151 benzodiazepines/or benzodiazepinones/ (23,660)

152 sedative antihistamine$.ti,ab. (61)

153 promethazine.ti,ab. (2061)

154 antidepressive agents/or benactyzine/or clorgyline/or deanol/or desvenlafaxine succinate/or duloxetine hydrochloride/or iproniazid/or isocarboxazid/or lithium carbonate/or lithium compounds/or moclobemide/or nialamide/ or phenelzine/or pizotyline/or rolipram/or sertraline/or tranylcypromine/or vilazodone hydrochloride/ (55,533)

155 Imipramine/ (9832)

156 mirtazapine.ti,ab. (1765) 157 antipsychotic agents/or acepromazine/or aripiprazole/or azaperone/or benperidol/or butaclamol/or chlorpromazine/ or chlorprothixene/or clopenthixol/or clozapine/or droperidol/or etazolate/or flupenthixol/or fluphenazine/or fluspirilene/or haloperidol/or loxapine/or lurasidone hydrochloride/or mesoridazine/or methiothepin/or methotrimeprazine/or molindone/ or ondansetron/or paliperidone palmitate/or penfluridol/or perazine/or perphenazine/or pimozide/or prochlorperazine/or promazine/or quetiapine fumarate/or raclopride/or remoxipride/or reserpine/or risperidone/or ritanserin/or spiperone/or sulpiride/or thioridazine/or thiothixene/or tiapride hydrochloride/or trifluoperazine/or trifluperidol/or triflupromazine/ (114,997)

158 olanzapine.ti,ab. (7555) 159 anticonvulsants/or acetazolamide/or bromides/or carbamazepine/or clonazepam/or clorazepate dipotassium/or diazepam/or dimethadione/or estazolam/or ethosuximide/or flunarizine/or lorazepam/or magnesium sulfate/or medazepam/or mephenytoin/or mephobarbital/or meprobamate/or nitrazepam/or paraldehyde/or phenobarbital/or phenytoin/or pregabalin/or primidone/or riluzole/or thiopental/or tiletamine/or trimethadione/or valproic acid/or vigabatrin/ (129,932)

160 antimanic agents/or lithium chloride/or lithium compounds/ (9229)

161 lamotrigine.ti,ab. (4632)

142

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TABLE 19 Search strategy for MEDLINE via Ovid (continued)

162 topiramate.ti,ab. (4045) 163 monoamine oxidase inhibitors/or chlorphenamidine/or clorgyline/or cuprizone/or furazolidone/or harmaline/or harmine/or isocarboxazid/or moclobemide/or monocrotophos/or pargyline/or selegiline/or tranylcypromine/ (17,953)

164 Prazosin/ (7567)

165 N-Methyl-3,4-methylenedioxyamphetamine/ (3644) 166 (MDMA or ecstasy).ti,ab. (5232)

167 148 or 149 or 150 or 151 or 152 or 153 or 154 or 155 or 156 or 157 or 158 or 159 or 160 or 161 or 162 or 163 or 164 or 165 or 166 (407,459)

168 86 and 147 (2717) 169 86 and 167 (405)

170 168 or 169 (3004)

171 limit 170 to yr=“1992 -Current” (2818)

PILOTS via ProQuest

Search date: 2 May 2017.

Two separate searches were conducted: one for psychological interventions and a second for pharmacological interventions.

Total records retrieved: 1981.

Date range searched: 1987 onwards.

TABLE 20 Search strategy for PILOTS via ProQuest

Set Search Results

Psychological interventions search strategy

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 143 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 20 Search strategy for PILOTS via ProQuest (continued)

Set Search Results

“Famine” OR “Fires” OR “Floods” OR “Home Accidents” OR “Hurricanes” OR “Industrial Accidents” OR “Landmines” OR “Landslides” OR “Lightning” OR “Motor Traffic Accidents” OR “Natural Disasters” OR “Nuclear Accidents” OR “Nuclear Testing” OR “Oil Spills” OR “Pedestrian Accidents” OR “Railroad Accidents” OR “Ship Accidents” OR “Technological Disasters” OR “Tornadoes” OR “Toxic Contamination” OR “Tsunamis” OR “Volcanoes”)) OR (humanitarian NEAR/1 (crisis OR crises)) OR (catastrophe OR catastrophic) OR SU.EXACT(“Survivors”) OR SU.EXACT(“Asylum Seekers” OR “Refugees”) OR ((forcibly OR internally) NEAR/1 displace*) OR (displace* NEAR/1 (people OR person* OR civilian*)) OR (victim* NEAR/2 (crime* OR disaster*)) OR (SU.EXACT(“Political Prisoners”)OR SU.EXACT(“Prisoners of War”)) OR SU.EXACT(“Military Personnel”) OR ((expose* OR exposure) NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (survivor* NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (victim* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare)) OR (witness* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare))

S2 (cognitive N2 therap*) OR (cognitive N2 treat*) OR (cognitive N1 rescript*) OR (cognitive N1 812° restructur*) OR CPT OR CBT OR TFCBT OR (trauma N2 CBT)

S4 (behav* N2 therap*) OR (behav* N2 treat*) OR (behav* N2 modif*) OR biofeedback OR 1077° neurofeedback OR “sensory feedback” OR “eye movement desensitization reprocessing” OR “eye movement desensitisation reprocessing” OR EMDR S6 (exposure N2 therap*) OR (exposure N2 treat*) OR “live exposure” OR “imaginal exposure” OR 223° “imaginal flooding” OR “exposure inhibition therapy” OR (implosive N2 therap*) OR “image habituation” OR “inoculation training”

S8 (acceptance N2 therap*) OR (commitment N2 therap*) OR hypnosis OR hypnotherap* OR 6900° mindfulness OR (supportive N2 therap*) OR (non-directive N2 counsel*) OR (nondirective N2 counsel*) OR psychotherapy OR “group therapy”

S9 (psychodynamic N1 therap*) OR (interpersonal psychotherap*) OR IPT OR (compassion N2 therap*) 756° OR “accelerated resolution” OR (sensorimotor N1 therap*) OR (schema N1 therap*)

S10 ((cognitive N2 therap*) OR (cognitive N2 treat*) OR (cognitive N1 rescript*) OR (cognitive N1 8207° restructur*) OR CPT OR CBT OR TFCBT OR (trauma N2 CBT)) OR ((behav* N2 therap*) OR (behav* N2 treat*) OR (behav* N2 modif*) OR biofeedback OR neurofeedback OR “sensory feedback” OR “eye movement desensitization reprocessing” OR “eye movement desensitisation reprocessing” OR EMDR) OR ((exposure N2 therap*) OR (exposure N2 treat*) OR “live exposure” OR “imaginal exposure” OR “imaginal flooding” OR “exposure inhibition therapy” OR (implosive N2 therap*) OR “image habituation” OR “inoculation training”) OR ((acceptance N2 therap*) OR (commitment N2 therap*) OR hypnosis OR hypnotherap* OR mindfulness OR (supportive N2 therap*) OR (non- directive N2 counsel*) OR (nondirective N2 counsel*) OR psychotherapy OR “group therapy”)OR ((psychodynamic N1 therap*) OR (interpersonal psychotherap*) OR IPT OR (compassion N2 therap*) OR “accelerated resolution” OR (sensorimotor N1 therap*) OR (schema N1 therap*))

S11 ((SU.EXACT(“Dating Violence”) OR SU.EXACT(“Interpersonal Violence”) OR SU.EXACT(“Family 5986° Violence”)) OR (batter* NEAR/2 (wife* OR wive* OR woman OR women OR men OR husband* OR partner*)) OR (physical* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (emotional* NEAR/ 1 abus*) OR (SU.EXACT(“Acquaintance Rape”) OR SU.EXACT(“Acquaintance Rape” OR “Partner Rape” OR “Rape”) OR SU.EXACT(“Partner Rape”)) OR (sexual* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR SU.EXACT(“Child Abuse”) OR (child* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (child* NEAR/2 (exploit* OR neglect* OR trauma*)) OR (“non accidental injur*” OR “non-accidental injur*” OR “nonaccidental injur*”) OR SU.EXACT(“Human Trafficking”) OR ((human OR person OR people) NEAR/2 (traffick* OR exploit*)) OR ((forced OR exploit*) NEAR/2 labour) OR SU.EXACT(“Slavery”) OR SU.EXACT(“Torture”) OR (slavery OR enslave* OR torture*) OR SU.EXACT (“Prostitution”) OR (prostitution* OR brothel*) OR (sex* NEAR/2 (exploit* OR traffick*)) OR SU.EXACT(“Terrorism”) OR SU.EXACT(“Chemical Warfare” OR “Civil Warfare” OR “Humanitarian Intervention” OR “Military Intervention” OR “War”) OR SU.EXACT(“Genocide”) OR (SU.EXACT(“War Neuroses”) OR SU.EXACT(“War Imprisonment”)) OR SU.EXACT(“Persecution”) OR (civil NEAR/1 (unrest OR conflict* OR disturbance* OR war OR wars OR warfare)) OR (persecution OR victimization OR victimisation) OR (captivity OR imprison*) OR SU.EXACT(“Concentration Camps”) OR (SU.EXACT(“Avalanches” OR “Blizzards” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Famine” OR “Floods” OR “Hurricanes” OR “Landslides” OR “Lightning” OR “Natural Disasters” OR “Tornadoes” OR “Tsunamis” OR “Volcanoes”) OR SU.EXACT(“Accidents” OR “Agent Orange” OR “Air Traffic Accidents” OR “Avalanches” OR “Blizzards” OR “Building Collapse” OR

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TABLE 20 Search strategy for PILOTS via ProQuest (continued)

Set Search Results

“Disasters” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Explosions” OR “Famine” OR “Fires” OR “Floods” OR “Home Accidents” OR “Hurricanes” OR “Industrial Accidents” OR “Landmines” OR “Landslides” OR “Lightning” OR “Motor Traffic Accidents” OR “Natural Disasters” OR “Nuclear Accidents” OR “Nuclear Testing” OR “Oil Spills” OR “Pedestrian Accidents” OR “Railroad Accidents” OR “Ship Accidents” OR “Technological Disasters” OR “Tornadoes” OR “Toxic Contamination” OR “Tsunamis” OR “Volcanoes”)) OR (humanitarian NEAR/1 (crisis OR crises)) OR (catastrophe OR catastrophic) OR SU.EXACT(“Survivors”) OR SU.EXACT(“Asylum Seekers” OR “Refugees”) OR ((forcibly OR internally) NEAR/1 displace*) OR (displace* NEAR/1 (people OR person* OR civilian*)) OR (victim* NEAR/2 (crime* OR disaster*)) OR (SU.EXACT(“Political Prisoners”)OR SU.EXACT(“Prisoners of War”)) OR SU.EXACT(“Military Personnel”) OR ((expose* OR exposure) NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (survivor* NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (victim* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare)) OR (witness* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare))) AND (((cognitive N2 therap*) OR (cognitive N2 treat*) OR (cognitive N1 rescript*) OR (cognitive N1 restructur*) OR CPT OR CBT OR TFCBT OR (trauma N2 CBT)) OR ((behav* N2 therap*) OR (behav* N2 treat*) OR (behav* N2 modif*) OR biofeedback OR neurofeedback OR “sensory feedback” OR “eye movement desensitization reprocessing” OR “eye movement desensitisation reprocessing” OR EMDR) OR ((exposure N2 therap*) OR (exposure N2 treat*) OR “live exposure” OR “imaginal exposure” OR “imaginal flooding” OR “exposure inhibition therapy” OR (implosive N2 therap*) OR “image habituation” OR “inoculation training”)OR ((acceptance N2 therap*) OR (commitment N2 therap*) OR hypnosis OR hypnotherap* OR mindfulness OR (supportive N2 therap*) OR (non-directive N2 counsel*) OR (nondirective N2 counsel*) OR psychotherapy OR “group therapy”) OR ((psychodynamic N1 therap*) OR (interpersonal psychotherap*) OR IPT OR (compassion N2 therap*) OR “accelerated resolution” OR (sensorimotor N1 therap*) OR (schema N1 therap*)))

S12 SU.EXACT(“Complex PTSD”) OR SU.EXACT(“PTSD”) 18,871°

S13 (((SU.EXACT(“Dating Violence”) OR SU.EXACT(“Interpersonal Violence”) OR SU.EXACT(“Family 1955° Violence”)) OR (batter* NEAR/2 (wife* OR wive* OR woman OR women OR men OR husband* OR partner*)) OR (physical* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (emotional* NEAR/1 abus*) OR (SU.EXACT(“Acquaintance Rape”) OR SU.EXACT(“Acquaintance Rape” OR “Partner Rape” OR “Rape”) OR SU.EXACT(“Partner Rape”)) OR (sexual* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR SU.EXACT(“Child Abuse”) OR (child* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (child* NEAR/2 (exploit* OR neglect* OR trauma*)) OR (“non accidental injur*” OR “non-accidental injur*” OR “nonaccidental injur*”) OR SU.EXACT(“Human Trafficking”) OR ((human OR person OR people) NEAR/2 (traffick* OR exploit*)) OR ((forced OR exploit*) NEAR/2 labour) OR SU.EXACT(“Slavery”) OR SU.EXACT(“Torture”) OR (slavery OR enslave* OR torture*) OR SU.EXACT (“Prostitution”) OR (prostitution* OR brothel*) OR (sex* NEAR/2 (exploit* OR traffick*)) OR SU.EXACT(“Terrorism”) OR SU.EXACT(“Chemical Warfare” OR “Civil Warfare” OR “Humanitarian Intervention” OR “Military Intervention” OR “War”) OR SU.EXACT(“Genocide”) OR (SU.EXACT(“War Neuroses”) OR SU.EXACT(“War Imprisonment”)) OR SU.EXACT(“Persecution”) OR (civil NEAR/1 (unrest OR conflict* OR disturbance* OR war OR wars OR warfare)) OR (persecution OR victimization OR victimisation) OR (captivity OR imprison*) OR SU.EXACT(“Concentration Camps”) OR (SU.EXACT(“Avalanches” OR “Blizzards” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Famine” OR “Floods” OR “Hurricanes” OR “Landslides” OR “Lightning” OR “Natural Disasters” OR “Tornadoes” OR “Tsunamis” OR “Volcanoes”) OR SU.EXACT(“Accidents” OR “Agent Orange” OR “Air Traffic Accidents” OR “Avalanches” OR “Blizzards” OR “Building Collapse” OR “Disasters” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Explosions” OR “Famine” OR “Fires” OR “Floods” OR “Home Accidents” OR “Hurricanes” OR “Industrial Accidents” OR “Landmines” OR “Landslides” OR “Lightning” OR “Motor Traffic Accidents” OR “Natural Disasters” OR “Nuclear Accidents” OR “Nuclear Testing” OR “Oil Spills” OR “Pedestrian Accidents” OR “Railroad Accidents” OR “Ship Accidents” OR “Technological Disasters” OR “Tornadoes” OR “Toxic Contamination” OR “Tsunamis” OR “Volcanoes”)) OR (humanitarian NEAR/1 (crisis OR crises)) OR (catastrophe OR catastrophic) OR SU.EXACT(“Survivors”) OR SU.EXACT(“Asylum Seekers” OR “Refugees”) OR ((forcibly OR internally) NEAR/1 displace*) OR (displace* NEAR/1 (people OR person* OR civilian*)) OR (victim* NEAR/2 (crime* OR disaster*)) OR (SU.EXACT(“Political Prisoners”)OR SU.EXACT(“Prisoners of War”)) OR SU.EXACT(“Military Personnel”) OR ((expose* OR exposure) NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (survivor* NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (victim* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare)) OR continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 145 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 20 Search strategy for PILOTS via ProQuest (continued)

Set Search Results

(witness* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare))) AND (((cognitive N2 therap*) OR (cognitive N2 treat*) OR (cognitive N1 rescript*) OR (cognitive N1 restructur*) OR CPT OR CBT OR TFCBT OR (trauma N2 CBT)) OR ((behav* N2 therap*) OR (behav* N2 treat*) OR (behav* N2 modif*) OR biofeedback OR neurofeedback OR “sensory feedback” OR “eye movement desensitization reprocessing” OR “eye movement desensitisation reprocessing” OR EMDR) OR ((exposure N2 therap*) OR (exposure N2 treat*) OR “live exposure” OR “imaginal exposure” OR “imaginal flooding” OR “exposure inhibition therapy” OR (implosive N2 therap*) OR “image habituation” OR “inoculation training”)OR ((acceptance N2 therap*) OR (commitment N2 therap*) OR hypnosis OR hypnotherap* OR mindfulness OR (supportive N2 therap*) OR (non-directive N2 counsel*) OR (nondirective N2 counsel*) OR psychotherapy OR “group therapy”) OR ((psychodynamic N1 therap*) OR (interpersonal psychotherap*) OR IPT OR (compassion N2 therap*) OR “accelerated resolution” OR (sensorimotor N1 therap*) OR (schema N1 therap*)))) AND (SU.EXACT(“Complex PTSD”) OR SU.EXACT(“PTSD”))

S14 (((SU.EXACT(“Dating Violence”) OR SU.EXACT(“Interpersonal Violence”) OR SU.EXACT(“Family Violence”)) OR (batter* NEAR/2 (wife* OR wive* OR woman OR women OR men OR husband* OR partner*)) OR (physical* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (emotional* NEAR/1 abus*) OR (SU.EXACT(“Acquaintance Rape”) OR SU.EXACT(“Acquaintance Rape” OR “Partner Rape” OR “Rape”) OR SU.EXACT(“Partner Rape”)) OR (sexual* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR SU.EXACT(“Child Abuse”) OR (child* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (child* NEAR/2 (exploit* OR neglect* OR trauma*)) OR (“non accidental injur*” OR “non-accidental injur*” OR “nonaccidental injur*”) OR SU.EXACT(“Human Trafficking”) OR ((human OR person OR people) NEAR/2 (traffick* OR exploit*)) OR ((forced OR exploit*) NEAR/2 labour) OR SU.EXACT(“Slavery”) OR SU.EXACT(“Torture”) OR (slavery OR enslave* OR torture*) OR SU.EXACT (“Prostitution”) OR (prostitution* OR brothel*) OR (sex* NEAR/2 (exploit* OR traffick*)) OR SU.EXACT(“Terrorism”) OR SU.EXACT(“Chemical Warfare” OR “Civil Warfare” OR “Humanitarian Intervention” OR “Military Intervention” OR “War”) OR SU.EXACT(“Genocide”) OR (SU.EXACT(“War Neuroses”) OR SU.EXACT(“War Imprisonment”)) OR SU.EXACT(“Persecution”) OR (civil NEAR/1 (unrest OR conflict* OR disturbance* OR war OR wars OR warfare)) OR (persecution OR victimization OR victimisation) OR (captivity OR imprison*) OR SU.EXACT(“Concentration Camps”) OR (SU.EXACT(“Avalanches” OR “Blizzards” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Famine” OR “Floods” OR “Hurricanes” OR “Landslides” OR “Lightning” OR “Natural Disasters” OR “Tornadoes” OR “Tsunamis” OR “Volcanoes”) OR SU.EXACT(“Accidents” OR “Agent Orange” OR “Air Traffic Accidents” OR “Avalanches” OR “Blizzards” OR “Building Collapse” OR “Disasters” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Explosions” OR “Famine” OR “Fires” OR “Floods” OR “Home Accidents” OR “Hurricanes” OR “Industrial Accidents” OR “Landmines” OR “Landslides” OR “Lightning” OR “Motor Traffic Accidents” OR “Natural Disasters” OR “Nuclear Accidents” OR “Nuclear Testing” OR “Oil Spills” OR “Pedestrian Accidents” OR “Railroad Accidents” OR “Ship Accidents” OR “Technological Disasters” OR “Tornadoes” OR “Toxic Contamination” OR “Tsunamis” OR “Volcanoes”)) OR (humanitarian NEAR/1 (crisis OR crises)) OR (catastrophe OR catastrophic) OR SU.EXACT(“Survivors”) OR SU.EXACT(“Asylum Seekers” OR “Refugees”) OR ((forcibly OR internally) NEAR/1 displace*) OR (displace* NEAR/1 (people OR person* OR civilian*)) OR (victim* NEAR/2 (crime* OR disaster*)) OR (SU.EXACT(“Political Prisoners”)OR SU.EXACT(“Prisoners of War”)) OR SU.EXACT(“Military Personnel”) OR ((expose* OR exposure) NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (survivor* NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (victim* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare)) OR (witness* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare))) AND (((cognitive N2 therap*) OR (cognitive N2 treat*) OR (cognitive N1 rescript*) OR (cognitive N1 restructur*) OR CPT OR CBT OR TFCBT OR (trauma N2 CBT)) OR ((behav* N2 therap*) OR (behav* N2 treat*) OR (behav* N2 modif*) OR biofeedback OR neurofeedback OR “sensory feedback” OR “eye movement desensitization reprocessing” OR “eye movement desensitisation reprocessing” OR EMDR) OR ((exposure N2 therap*) OR (exposure N2 treat*) OR “live exposure” OR “imaginal exposure” OR “imaginal flooding” OR “exposure inhibition therapy” OR (implosive N2 therap*) OR “image habituation” OR “inoculation training”)OR ((acceptance N2 therap*) OR (commitment N2 therap*) OR hypnosis OR hypnotherap* OR mindfulness OR (supportive N2 therap*) OR (non-directive N2 counsel*) OR (nondirective N2 counsel*) OR psychotherapy OR “group therapy”) OR ((psychodynamic N1 therap*) OR (interpersonal psychotherap*) OR IPT OR (compassion N2 therap*) OR “accelerated resolution” OR (sensorimotor N1 therap*) OR (schema N1 therap*)))) AND (SU.EXACT(“Complex PTSD”) OR SU.EXACT(“PTSD”)) Limits applied

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TABLE 20 Search strategy for PILOTS via ProQuest (continued)

Set Search Results

Pharmacological interventions search strategy

S1 (SU.EXACT(“Dating Violence”) OR SU.EXACT(“Interpersonal Violence”) OR SU.EXACT(“Family 43,537° Violence”)) OR (batter* NEAR/2 (wife* OR wive* OR woman OR women OR men OR husband* OR partner*)) OR (physical* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (emotional* NEAR/1 abus*) OR (SU.EXACT(“Acquaintance Rape”) OR SU.EXACT(“Acquaintance Rape” OR “Partner Rape” OR “Rape”) OR SU.EXACT(“Partner Rape”)) OR (sexual* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR SU.EXACT(“Child Abuse”) OR (child* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (child* NEAR/2 (exploit* OR neglect* OR trauma*)) OR (“non accidental injur*” OR “non-accidental injur*” OR “nonaccidental injur*”) OR SU.EXACT(“Human Trafficking”) OR ((human OR person OR people) NEAR/2 (traffick* OR exploit*)) OR ((forced OR exploit*) NEAR/2 labour) OR SU.EXACT(“Slavery”) OR SU.EXACT(“Torture”) OR (slavery OR enslave* OR torture*) OR SU.EXACT (“Prostitution”) OR (prostitution* OR brothel*) OR (sex* NEAR/2 (exploit* OR traffick*)) OR SU.EXACT(“Terrorism”) OR SU.EXACT(“Chemical Warfare” OR “Civil Warfare” OR “Humanitarian Intervention” OR “Military Intervention” OR “War”) OR SU.EXACT(“Genocide”) OR (SU.EXACT(“War Neuroses”) OR SU.EXACT(“War Imprisonment”)) OR SU.EXACT(“Persecution”) OR (civil NEAR/1 (unrest OR conflict* OR disturbance* OR war OR wars OR warfare)) OR (persecution OR victimization OR victimisation) OR (captivity OR imprison*) OR SU.EXACT(“Concentration Camps”) OR (SU.EXACT(“Avalanches” OR “Blizzards” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Famine” OR “Floods” OR “Hurricanes” OR “Landslides” OR “Lightning” OR “Natural Disasters” OR “Tornadoes” OR “Tsunamis” OR “Volcanoes”) OR SU.EXACT(“Accidents” OR “Agent Orange” OR “Air Traffic Accidents” OR “Avalanches” OR “Blizzards” OR “Building Collapse” OR “Disasters” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Explosions” OR “Famine” OR “Fires” OR “Floods” OR “Home Accidents” OR “Hurricanes” OR “Industrial Accidents” OR “Landmines” OR “Landslides” OR “Lightning” OR “Motor Traffic Accidents” OR “Natural Disasters” OR “Nuclear Accidents” OR “Nuclear Testing” OR “Oil Spills” OR “Pedestrian Accidents” OR “Railroad Accidents” OR “Ship Accidents” OR “Technological Disasters” OR “Tornadoes” OR “Toxic Contamination” OR “Tsunamis” OR “Volcanoes”)) OR (humanitarian NEAR/1 (crisis OR crises)) OR (catastrophe OR catastrophic) OR SU.EXACT(“Survivors”) OR SU.EXACT(“Asylum Seekers” OR “Refugees”) OR ((forcibly OR internally) NEAR/1 displace*) OR (displace* NEAR/1 (people OR person* OR civilian*)) OR (victim* NEAR/2 (crime* OR disaster*)) OR (SU.EXACT(“Political Prisoners”)OR SU.EXACT(“Prisoners of War”)) OR SU.EXACT(“Military Personnel”) OR ((expose* OR exposure) NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (survivor* NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (victim* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare)) OR (witness* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare))

S12 SU.EXACT(“Complex PTSD”) OR SU.EXACT(“PTSD”) 18,871° S13 ((SU.EXACT(“Dating Violence”) OR SU.EXACT(“Interpersonal Violence”) OR SU.EXACT(“Family 13,010° Violence”)) OR (batter* NEAR/2 (wife* OR wive* OR woman OR women OR men OR husband* OR partner*)) OR (physical* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (emotional* NEAR/1 abus*) OR (SU.EXACT(“Acquaintance Rape”) OR SU.EXACT(“Acquaintance Rape” OR “Partner Rape” OR “Rape”) OR SU.EXACT(“Partner Rape”)) OR (sexual* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR SU.EXACT(“Child Abuse”) OR (child* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (child* NEAR/2 (exploit* OR neglect* OR trauma*)) OR (“non accidental injur*” OR “non-accidental injur*” OR “nonaccidental injur*”) OR SU.EXACT(“Human Trafficking”) OR ((human OR person OR people) NEAR/2 (traffick* OR exploit*)) OR ((forced OR exploit*) NEAR/2 labour) OR SU.EXACT(“Slavery”) OR SU.EXACT(“Torture”) OR (slavery OR enslave* OR torture*) OR SU.EXACT (“Prostitution”) OR (prostitution* OR brothel*) OR (sex* NEAR/2 (exploit* OR traffick*)) OR SU.EXACT(“Terrorism”) OR SU.EXACT(“Chemical Warfare” OR “Civil Warfare” OR “Humanitarian Intervention” OR “Military Intervention” OR “War”) OR SU.EXACT(“Genocide”) OR (SU.EXACT(“War Neuroses”) OR SU.EXACT(“War Imprisonment”)) OR SU.EXACT(“Persecution”) OR (civil NEAR/1 (unrest OR conflict* OR disturbance* OR war OR wars OR warfare)) OR (persecution OR victimization OR victimisation) OR (captivity OR imprison*) OR SU.EXACT(“Concentration Camps”) OR (SU.EXACT(“Avalanches” OR “Blizzards” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Famine” OR “Floods” OR “Hurricanes” OR “Landslides” OR “Lightning” OR “Natural Disasters” OR “Tornadoes” OR “Tsunamis” OR “Volcanoes”) OR SU.EXACT(“Accidents” OR “Agent Orange” OR “Air Traffic Accidents” OR “Avalanches” OR “Blizzards” OR “Building Collapse” OR “Disasters” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Explosions” OR “Famine” OR “Fires” OR “Floods” OR “Home Accidents” OR “Hurricanes” OR “Industrial Accidents” OR “Landmines” OR “Landslides” OR “Lightning” OR “Motor Traffic Accidents” OR “Natural Disasters” continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 147 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 20 Search strategy for PILOTS via ProQuest (continued)

Set Search Results

OR “Nuclear Accidents” OR “Nuclear Testing” OR “Oil Spills” OR “Pedestrian Accidents” OR “Railroad Accidents” OR “Ship Accidents” OR “Technological Disasters” OR “Tornadoes” OR “Toxic Contamination” OR “Tsunamis” OR “Volcanoes”)) OR (humanitarian NEAR/1 (crisis OR crises)) OR (catastrophe OR catastrophic) OR SU.EXACT(“Survivors”) OR SU.EXACT(“Asylum Seekers” OR “Refugees”) OR ((forcibly OR internally) NEAR/1 displace*) OR (displace* NEAR/1 (people OR person* OR civilian*)) OR (victim* NEAR/2 (crime* OR disaster*)) OR (SU.EXACT(“Political Prisoners”)OR SU.EXACT(“Prisoners of War”)) OR SU.EXACT(“Military Personnel”) OR ((expose* OR exposure) NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (survivor* NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (victim* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare)) OR (witness* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare))) AND (SU.EXACT(“Complex PTSD”) OR SU.EXACT(“PTSD”))

S14 alprazolam or amobarbital or azaperone or barbital or bromisovalum or chloral hydrate or chloralose 77° or chlordiazepoxide or chlormethiazole or dexmedetomidine or diazepam or diphenhydramine or eszopiclone or ethchlorvynol or etomidate or etorphine or flurazepam or glutethimide or hexobarbital or lorazepam or medazepam or medetomidine or mephobarbital or meprobamate or methapyrilene or methaqualone or midazolam or nitrazepam or oxazepam or paraldehyde or pentobarbital or phenobarbital or propofol or secobarbital or temazepam or thiamylal or thiopental or xylazine

S15 bromazepam or buspirone or chlormezanone or clorazepate dipotassium or estazolam or 84° flunitrazepam or fluvoxamine or nordazepam or ondansetron or oxprenolol or prazepam or pregabalin or ritanserin or tranylcypromine or trazodone or triazolam or zolazepam

S16 benzodiazepines or benzodiazepinones or promethazine or benactyzine or clorgyline or deanol or 547° desvenlafaxine succinate or duloxetine hydrochloride or iproniazid or isocarboxazid or lithium carbonate or lithium compounds or moclobemide or nialamide or phenelzine or pizotyline or rolipram or sertraline or tranylcypromine or vilazodone hydrochloride or Imipramine or mirtazapine

S17 acepromazine or aripiprazole or azaperone or benperidol or butaclamol or chlorpromazine or 107° chlorprothixene or clopenthixol or clozapine or droperidol or etazolate or flupenthixol or fluphenazine or fluspirilene or haloperidol or loxapine or lurasidone hydrochloride or mesoridazine or methiothepin or methotrimeprazine or molindone or ondansetron or paliperidone palmitate or penfluridol or perazine or perphenazine or pimozide or prochlorperazine or promazine or quetiapine fumarate or raclopride or remoxipride or reserpine or risperidone or ritanserin or spiperone or sulpiride or thioridazine or thiothixene or tiapride hydrochloride or trifluoperazine or trifluperidol or triflupromazine or olanzapine

S18 acetazolamide or bromides or carbamazepine or clonazepam or clorazepate dipotassium or diazepam 145° or dimethadione or estazolam or ethosuximide or flunarizine or lorazepam or magnesium sulfate or medazepam or mephenytoin or mephobarbital or meprobamate or nitrazepam or paraldehyde or phenobarbital or phenytoin or pregabalin or primidone or riluzole or thiopental or tiletamine or trimethadione or valproic acid or vigabatrin or lithium chloride or lithium compounds or lamotrigine or topiramate

S19 monoamine oxidase inhibitors or chlorphenamidine or clorgyline or cuprizone or furazolidone or 197° harmaline or harmine or isocarboxazid or moclobemide or monocrotophos or pargyline or selegiline or tranylcypromine or Prazosin or N-Methyl-3,4-methylenedioxyamphetamine or MDMA or ecstasy

S20 hypnotics OR (hypnotic drugs) OR sedatives OR (sedative drugs) OR “anti-anxiety drug*” OR “anti- 413° anxiety agent*” OR “antidepressive agent*” OR “antidepressive drug*” OR “antipsychotic agent*” OR “antipsychotic drug*”

S21 “antimanic agent*” OR “antimanic drug*” OR anticonvulsants OR “anticonvulsant drug*” OR “z drug*” 176°

S22 (alprazolam or amobarbital or azaperone or barbital or bromisovalum or chloral hydrate or chloralose 1302° or chlordiazepoxide or chlormethiazole or dexmedetomidine or diazepam or diphenhydramine or eszopiclone or ethchlorvynol or etomidate or etorphine or flurazepam or glutethimide or hexobarbital or lorazepam or medazepam or medetomidine or mephobarbital or meprobamate or methapyrilene or methaqualone or midazolam or nitrazepam or oxazepam or paraldehyde or pentobarbital or phenobarbital or propofol or secobarbital or temazepam or thiamylal or thiopental or xylazine) OR (bromazepam or buspirone or chlormezanone or clorazepate dipotassium or estazolam or flunitrazepam or fluvoxamine or nordazepam or ondansetron or oxprenolol or prazepam or pregabalin or ritanserin or tranylcypromine or trazodone or triazolam or zolazepam) OR (benzodiazepines or benzodiazepinones or promethazine or benactyzine or clorgyline or deanol or desvenlafaxine succinate or duloxetine hydrochloride or iproniazid or isocarboxazid or lithium

148

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TABLE 20 Search strategy for PILOTS via ProQuest (continued)

Set Search Results

carbonate or lithium compounds or moclobemide or nialamide or phenelzine or pizotyline or rolipram or sertraline or tranylcypromine or vilazodone hydrochloride or Imipramine or mirtazapine) OR (acepromazine or aripiprazole or azaperone or benperidol or butaclamol or chlorpromazine or chlorprothixene or clopenthixol or clozapine or droperidol or etazolate or flupenthixol or fluphenazine or fluspirilene or haloperidol or loxapine or lurasidone hydrochloride or mesoridazine or methiothepin or methotrimeprazine or molindone or ondansetron or paliperidone palmitate or penfluridol or perazine or perphenazine or pimozide or prochlorperazine or promazine or quetiapine fumarate or raclopride or remoxipride or reserpine or risperidone or ritanserin or spiperone or sulpiride or thioridazine or thiothixene or tiapride hydrochloride or trifluoperazine or trifluperidol or triflupromazine or olanzapine) OR (acetazolamide or bromides or carbamazepine or clonazepam or clorazepate dipotassium or diazepam or dimethadione or estazolam or ethosuximide or flunarizine or lorazepam or magnesium sulfate or medazepam or mephenytoin or mephobarbital or meprobamate or nitrazepam or paraldehyde or phenobarbital or phenytoin or pregabalin or primidone or riluzole or thiopental or tiletamine or trimethadione or valproic acid or vigabatrin or lithium chloride or lithium compounds or lamotrigine or topiramate) OR (monoamine oxidase inhibitors or chlorphenamidine or clorgyline or cuprizone or furazolidone or harmaline or harmine or isocarboxazid or moclobemide or monocrotophos or pargyline or selegiline or tranylcypromine or Prazosin or N-Methyl-3,4- methylenedioxyamphetamine or MDMA or ecstasy) OR (hypnotics OR (hypnotic drugs) OR sedatives OR (sedative drugs) OR “anti-anxiety drug*” OR “anti-anxiety agent*” OR “antidepressive agent*” OR “antidepressive drug*” OR “antipsychotic agent*” OR “antipsychotic drug*”)OR(“antimanic agent*” OR “antimanic drug*” OR anticonvulsants OR “anticonvulsant drug*” OR “z drug*”)

S23 (((SU.EXACT(“Dating Violence”)ORSU.EXACT(“Interpersonal Violence”)ORSU.EXACT(“Family Violence”)) 199° OR (batter* NEAR/2 (wife* OR wive* OR woman OR women OR men OR husband* OR partner*)) OR (physical* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (emotional* NEAR/1 abus*) OR (SU.EXACT(“Acquaintance Rape”)ORSU.EXACT(“Acquaintance Rape” OR “Partner Rape” OR “Rape”) OR SU.EXACT(“Partner Rape”)) OR (sexual* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR SU.EXACT(“Child Abuse”) OR (child* NEAR/2 (abus* OR assault* OR violen* OR aggress*)) OR (child* NEAR/2 (exploit* OR neglect* OR trauma*)) OR (“non accidental injur*” OR “non-accidental injur*” OR “nonaccidental injur*”)ORSU.EXACT(“Human Trafficking”) OR ((human OR person OR people) NEAR/2 (traffick* OR exploit*)) OR ((forced OR exploit*) NEAR/2 labour) OR SU.EXACT(“Slavery”)ORSU.EXACT (“Torture”)OR(slaveryORenslave*ORtorture*)ORSU.EXACT(“Prostitution”) OR (prostitution* OR brothel*) OR (sex* NEAR/2 (exploit* OR traffick*)) OR SU.EXACT(“Terrorism”)ORSU.EXACT(“Chemical Warfare” OR “Civil Warfare” OR “Humanitarian Intervention” OR “Military Intervention” OR “War”) OR SU.EXACT(“Genocide”)OR(SU.EXACT(“War Neuroses”)ORSU.EXACT(“War Imprisonment”)) OR SU.EXACT(“Persecution”) OR (civil NEAR/1 (unrest OR conflict* OR disturbance* OR war OR wars OR warfare)) OR (persecution OR victimization OR victimisation) OR (captivity OR imprison*) OR SU.EXACT (“Concentration Camps”)OR(SU.EXACT(“Avalanches” OR “Blizzards” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Famine” OR “Floods” OR “Hurricanes” OR “Landslides” OR “Lightning” OR “Natural Disasters” OR “Tornadoes” OR “Tsunamis” OR “Volcanoes”)ORSU.EXACT(“Accidents” OR “Agent Orange” OR “Air Traffic Accidents” OR “Avalanches” OR “Blizzards” OR “Building Collapse” OR “Disasters” OR “Drought” OR “Earthquakes” OR “Epidemics” OR “Epizootics” OR “Explosions” OR “Famine” OR “Fires” OR “Floods” OR “Home Accidents” OR “Hurricanes” OR “Industrial Accidents” OR “Landmines” OR “Landslides” OR “Lightning” OR “Motor Traffic Accidents” OR “Natural Disasters” OR “Nuclear Accidents” OR “Nuclear Testing” OR “Oil Spills” OR “Pedestrian Accidents” OR “Railroad Accidents” OR “Ship Accidents” OR “Technological Disasters” OR “Tornadoes” OR “Toxic Contamination” OR “Tsunamis” OR “Volcanoes”)) OR (humanitarian NEAR/1 (crisis OR crises)) OR (catastrophe OR catastrophic) OR SU.EXACT (“Survivors”)ORSU.EXACT(“Asylum Seekers” OR “Refugees”) OR ((forcibly OR internally) NEAR/1 displace*) OR (displace* NEAR/1 (people OR person* OR civilian*)) OR (victim* NEAR/2 (crime* OR disaster*)) OR (SU.EXACT(“Political Prisoners”)ORSU.EXACT(“Prisoners of War”)) OR SU.EXACT(“Military Personnel”) OR ((expose* OR exposure) NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (survivor* NEAR/2 (abuse OR assault* OR disaster* OR terror* OR torture* OR trauma* OR rape OR violen* OR war OR warfare)) OR (victim* NEAR/ 2(abuseORassault*ORcrimeORdisaster*ORrapeORterror*ORtorture*ORtrauma*ORviolen*OR war OR warfare)) OR (witness* NEAR/2 (abuse OR assault* OR crime OR disaster* OR rape OR terror* OR torture* OR trauma* OR violen* OR war OR warfare))) AND (SU.EXACT(“Complex PTSD”)ORSU.EXACT (“PTSD”))) AND ((alprazolam or amobarbital or azaperone or barbital or bromisovalum or chloral hydrate or chloralose or chlordiazepoxide or chlormethiazole or dexmedetomidine or diazepam or diphenhydramine or eszopiclone or ethchlorvynol or etomidate or etorphine or flurazepam or glutethimide or hexobarbital or lorazepam or medazepam or medetomidine or mephobarbital or meprobamate or methapyrilene or methaqualone or midazolam or nitrazepam or oxazepam or paraldehyde or pentobarbital or phenobarbital or propofol or secobarbital or temazepam or thiamylal or thiopental or xylazine) OR (bromazepam or buspirone or chlormezanone or clorazepate dipotassium or estazolam or flunitrazepam or fluvoxamine or continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 149 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 20 Search strategy for PILOTS via ProQuest (continued)

Set Search Results

nordazepam or ondansetron or oxprenolol or prazepam or pregabalin or ritanserin or tranylcypromine or trazodone or triazolam or zolazepam) OR (benzodiazepines or benzodiazepinones or promethazine or benactyzine or clorgyline or deanol or desvenlafaxine succinate or duloxetine hydrochloride or iproniazid or isocarboxazid or lithium carbonate or lithium compounds or moclobemide or nialamide or phenelzine or pizotyline or rolipram or sertraline or tranylcypromine or vilazodone hydrochloride or Imipramine or mirtazapine) OR (acepromazine or aripiprazole or azaperone or benperidol or butaclamol or chlorpromazine or chlorprothixene or clopenthixol or clozapine or droperidol or etazolate or flupenthixol or fluphenazine or fluspirilene or haloperidol or loxapine or lurasidone hydrochloride or mesoridazine or methiothepin or methotrimeprazine or molindone or ondansetron or paliperidone palmitate or penfluridol or perazine or perphenazine or pimozide or prochlorperazine or promazine or quetiapine fumarate or raclopride or remoxipride or reserpine or risperidone or ritanserin or spiperone or sulpiride or thioridazine or thiothixene or tiapride hydrochloride or trifluoperazine or trifluperidol or triflupromazine or olanzapine) OR (acetazolamide or bromides or carbamazepine or clonazepam or clorazepate dipotassium or diazepam or dimethadione or estazolam or ethosuximide or flunarizine or lorazepam or magnesium sulfate or medazepam or mephenytoin or mephobarbital or meprobamate or nitrazepam or paraldehyde or phenobarbital or phenytoin or pregabalin or primidone or riluzole or thiopental or tiletamine or trimethadione or valproic acid or vigabatrin or lithium chloride or lithium compounds or lamotrigine or topiramate) OR (monoamine oxidase inhibitors or chlorphenamidine or clorgyline or cuprizone or furazolidone or harmaline or harmine or isocarboxazid or moclobemide or monocrotophos or pargyline or selegiline or tranylcypromine or Prazosin or N-Methyl-3,4-methylenedioxyamphetamine or MDMA or ecstasy) OR (hypnotics OR (hypnotic drugs) OR sedatives OR (sedative drugs) OR “anti-anxiety drug*” OR “anti-anxiety agent*” OR “antidepressive agent*” OR “antidepressive drug*” OR “antipsychotic agent*” OR “antipsychotic drug*”)OR(“antimanic agent*” OR “antimanic drug*” OR anticonvulsants OR “anticonvulsant drug*” OR “zdrug*”))

PsycINFO via Ovid

Search date: 18 April 2017.

Records retrieved: 2658.

Date range searched: 1806 to April week 2 2017.

TABLE 21 Search strategy for PsycINFO via Ovid

1 exp Violence/ (66,551)

2 Exposure to Violence/ (509)

3 violence.ti,ab. (60,703)

4 Domestic Violence/ (10,282)

5 Intimate Partner Violence/ (5917)

6 Battered Females/ (3011)

7 Partner Abuse/ (4576) 8 (batter$ adj2 (wife$ or wive$ or woman or women or men or husband$ or partner$)).ti,ab. (2311)

9 Physical Abuse/ (5465)

10 (physical$ adj2 (abus$ or assault$ or violen$ or aggress$)).ti,ab. (14,559)

11 Emotional Abuse/ (2267)

12 (emotional$ adj2 abus$).ti,ab. (2704)

150

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TABLE 21 Search strategy for PsycINFO via Ovid (continued)

13 Rape/ (5043) 14 rape.ti,ab. (7403)

15 (sexual$ adj2 (abus$ or assault$ or violen$ or aggress$)).ti,ab. (30,943)

16 Child Abuse/ (26,161)

17 Sexual Abuse/ (18,589)

18 child$ sexual abuse.ti,ab. (8393)

19 Incest/ (2526)

20 (child$ adj2 exploit$).ti,ab. (354) 21 Child Neglect/ (3628)

22 child neglect.ti,ab. (642)

23 (child$ adj2 trauma).ti,ab. (4693)

24 (non accidental injur$ or non-accidental injur$ or nonaccidental injur$).ti,ab. (48)

25 Human Trafficking/ (595)

26 ((human or person or people) adj2 (traffick$ or exploit$)).ti,ab. (543)

27 ((forced or exploit$) adj2 labour).ti,ab. (40) 28 Slavery/ (215)

29 Torture/ (1151)

30 (slavery or torture$ or enslave$).ti,ab. (3946)

31 Prostitution/ (2998)

32 (prostitut$ or brothel$).ti,ab. (2805)

33 (sex$ adj2 (exploit$ or traffick$)).ti,ab. (1080)

34 Terrorism/ (6711)

35 (terrorism or terrorist$).ti,ab. (7151) 36 political terror$.ti,ab. (71)

37 Torture/ (1151)

38 War/ (12,259)

39 Combat Experience/ (2479)

40 Genocide/ (899)

41 Holocaust/ (1199)

42 Mass Murder/ (84) 43 (civil adj (unrest or conflict$ or disturbance$ or war or wars or warfare)).ti,ab. (1682)

44 (persecution or victimization or victimisation).ti,ab. (15,549)

45 (captivity or imprison$ or concentration camp$).ti,ab. (5516)

46 exp Disasters/ (7760)

47 Natural Disasters/ (4227)

48 natural disaster$.ti,ab. (2344)

49 (earthquake$ or tsunami$).ti,ab. (2820) 50 (humanitarian adj (crisis or crises)).ti,ab. (106) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 151 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 21 Search strategy for PsycINFO via Ovid (continued)

51 (catastrophe$ or catastrophic event$ or catastrophic experience$).ti,ab. (1943) 52 exp Survivors/ (11,959)

53 Holocaust Survivors/ (1105)

54 Refugees/ (4568)

55 (asylum seeker$ or refugee$ or migrant$).ti,ab. (13,548)

56 ((forcibly or internally) adj displace$).ti,ab. (237)

57 (displace$ adj (people or person$ or civilian$)).ti,ab. (408)

58 Crime Victims/ (4167) 59 Victimization/ (18,276)

60 Prisoners/ (9692)

61 “Prisoners of War”/ (472)

62 Slavery/ (215)

63 Military Veterans/ (10,341)

64 ((expose$ or exposure) adj2 (abuse or assault$ or disaster$ or terror$ or torture$ or trauma$ or rape or violen$ or war or warfare)).ti,ab. (9024)

65 (survivor$ adj2 (abuse or assault$ or disaster$ or terror$ or torture$ or trauma$ or rape or violen$ or war or warfare)).ti,ab. (4321)

66 (victim$ adj2 (abuse or assault$ or crime or disaster$ or rape or terror$ or torture$ or trauma$ or violen$ or war or warfare)).ti,ab. (9727)

67 (witness$ adj2 (abuse or assault$ or disaster$ or rape or terror$ or torture$ or trauma$ or violen$ or war or warfare)).ti,ab. (1747)

68 1or2or3or4or5or6or7or8or9or10or11or12or13or14or15or16or17or18or19or20or21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 or 62 or 63 or 64 or 65 or 66 or 67 (213,458)

69 exp Posttraumatic Stress Disorder/ (27,018)

70 Complex PTSD/ (123)

71 DESNOS/ (15) 72 “Disorders of Extreme Distress Not Otherwise Specified”.ti,ab. (0)

73 (PTSD or CPTSD).ti,ab. (25,381)

74 posttrauma$.ti,ab. (26,998)

75 post-trauma$.ti,ab. (11,564)

76 “post trauma$”.ti,ab. (11,564)

77 post traumatic stress.ti,ab. (8923)

78 post traumatic stress.id. (2783) 79 combat stress$.ti,ab. (497)

80 combat disorder$.ti,ab. (12)

81 DESNOS.ti,ab. (54)

82 complex trauma$.ti,ab. (515)

83 (complex adj2 trauma$).ti,ab. (689)

84 traumatic stress.ti,ab. (11,630)

85 traumatic memor$.ti,ab. (1290)

152

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TABLE 21 Search strategy for PsycINFO via Ovid (continued)

86 traumatization.ti,ab. (1511) 87 traumatisation.ti,ab. (154)

88 (trauma adj2 (expos$ or event$ or experienc$)).ti,ab. (6634)

89 69 or 70 or 71 or 72 or 73 or 74 or 75 or 76 or 77 or 78 or 79 or 80 or 81 or 82 or 83 or 84 or 85 or 86 or 87 or 88 (47,567) 90 68 and 89 (25,142)

91 exp Cognitive Therapy/ (12,639)

92 cognitive behaviour$ therapy.ti,ab. (3854)

93 cognitive behavior$ therapy.ti,ab. (13,015)

94 cognitive restructuring.ti,ab. (2074)

95 cognitive rescripting.ti,ab. (0)

96 cognitive processing therapy.ti,ab. (272) 97 CPT.ti,ab. (1922)

98 cognitive therapy.ti,ab. (5335)

99 cognitive behavioural treatment$.ti,ab. (520)

100 cognitive behavioral treatment$.ti,ab. (2997)

101 (CBT or TFCBT).ti,ab. (10,616)

102 cognitive trauma therapy.ti,ab. (8)

103 trauma focus$ CBT.ti,ab. (57) 104 91 or 92 or 93 or 94 or 95 or 96 or 97 or 98 or 99 or 100 or 101 or 102 or 103 (33,767)

105 exp Behavior Therapy/ (18,509)

106 (behavior$ adj2 (therap$ or treat$ or modif$)).ti,ab. (41,822)

107 (behaviour$ adj2 (therap$ or treat$ or modif$)).ti,ab. (7365)

108 (dialectical behavio$ therap$ or dialectical behavio$ treat$).ti,ab. (1461)

109 DBT.ti,ab. (1135)

110 biofeedback, psychology/or feedback, sensory/or neurofeedback/ (1205) 111 (biofeedback or neurofeedback or sensory feedback).ti,ab. (6695)

112 desensitization, psychologic/or eye movement desensitization reprocessing/or implosive therapy/or virtual reality exposure therapy/ (421)

113 (psychological adj2 desensiti$).ti,ab. (5) 114 Eye Movement Desensitization Therapy/ (1230)

115 eye movement desensiti?ation reprocessing.ti,ab. (61)

116 EMDR.ti,ab. (1346)

117 Exposure Therapy/ (1979)

118 (exposure adj (therap$ or treat$)).ti,ab. (2200)

119 prolonged exposure therap$.ti,ab. (151)

120 live exposure.ti,ab. (22) 121 imaginal exposure.ti,ab. (280)

122 imaginal flooding.ti,ab. (35) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 153 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 21 Search strategy for PsycINFO via Ovid (continued)

123 exposure inhibition therap$.ti,ab. (1) 124 implosive therap$.ti,ab. (143)

125 image habituation.ti,ab. (5)

126 inoculation training.ti,ab. (292)

127 105 or 106 or 107 or 108 or 109 or 110 or 111 or 112 or 113 or 114 or 115 or 116 or 117 or 118 or 119 or 120 or 121 or 122 or 123 or 124 or 125 or 126 (65,864)

128 (acceptance adj2 therap$).ti,ab. (376)

129 (commitment adj2 therap$).ti,ab. (1501)

130 Hypnosis/ (7091)

131 (hypnosis or hypnotherap$).ti,ab. (11,623)

132 Mindfulness/ (6583)

133 mindfulness.ti,ab. (8091) 134 (supportive adj (therap$ or psychotherap$)).ti,ab. (1490)

135 (non-directive adj (counselling or counseling)).ti,ab. (81)

136 (nondirective adj (counselling or counseling)).ti,ab. (113)

137 (non directive adj (counselling or counseling)).ti,ab. (81)

138 psychodynamic therap$.ti,ab. (1317)

139 inter personal psychotherap$.ti,ab. (1)

140 interpersonal psychotherap$.ti,ab. (1197) 141 interpersonal therapy.ti,ab. (512)

142 IPT.ti,ab. (974)

143 (compassion adj2 therap$).ti,ab. (105)

144 accelerated resolution.ti,ab. (8)

145 sensorimotor therap$.ti,ab. (11)

146 schema therapy.ti,ab. (312)

147 Stress Management/ (4566) 148 Supportive Psychotherapy/ (480)

149 Group Psychotherapy/ (18,367)

150 Counseling/ (21,293)

151 (non-directive counsel$ or non directive counsel$ or nondirective counsel$).ti,ab. (197)

152 compassion therap$.ti,ab. (4)

153 128 or 129 or 130 or 131 or 132 or 133 or 134 or 135 or 136 or 137 or 138 or 139 or 140 or 141 or 142 or 143 or 144 or 145 or 146 or 147 or 148 or 149 or 150 or 151 or 152 (71,049)

154 104 or 127 or 153 (140,028)

155 hypnotic drugs/or amobarbital/or apomorphine/or barbital/or chloral hydrate/or codeine/or flurazepam/or glutethimide/or hexobarbital/or meprobamate/or methaqualone/or nitrazepam/or pentobarbital/or phenobarbital/or secobarbital/or thalidomide/or thiopental/or triazolam/ (5588)

156 hypnotics.ti,ab. (1574) 157 hypnotic drug$.ti,ab. (399)

158 z drug$.ti,ab. (43)

154

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TABLE 21 Search strategy for PsycINFO via Ovid (continued)

159 tranquilizing drugs/or amitriptyline/or benactyzine/or doxepin/or haloperidol/or meprobamate/or minor tranquilizers/or neuroleptic drugs/or phenothiazine derivatives/or pimozide/or thiothixene/ (27,445)

160 exp benzodiazepines/ (9874)

161 sedative antihistamine$.ti,ab. (13)

162 promethazine.ti,ab. (184) 163 antidepressant drugs/or bupropion/or citalopram/or fluoxetine/or fluvoxamine/or iproniazid/or isocarboxazid/or lithium carbonate/or methylphenidate/or mianserin/or moclobemide/or molindone/or nefazodone/or nialamide/or nomifensine/or paroxetine/or phenelzine/or pheniprazine/or pipradrol/or serotonin norepinephrine reuptake inhibitors/ or sertraline/or sulpiride/or tranylcypromine/or trazodone/or tricyclic antidepressant drugs/or venlafaxine/or zimeldine/ (31,904)

164 Imipramine.ti,ab. (3980)

165 mirtazapine.ti,ab. (1112)

166 neuroleptic drugs/or aripiprazole/or clozapine/or molindone/or nialamide/or olanzapine/or quetiapine/or reserpine/or risperidone/or spiroperidol/or sulpiride/or tetrabenazine/ (28,386)

167 mood stabilizers/or anticonvulsive drugs/or carbamazepine/or lithium/or valproic acid/ (13,520)

168 mood stabilisers.ti,ab. (141)

169 antiepileptics.ti,ab. (305) 170 lamotrigine.ti,ab. (1792)

171 topiramate.ti,ab. (1494)

172 valproate.ti,ab. (2781)

173 monoamine oxidase inhibitors/or iproniazid/or isocarboxazid/or moclobemide/or nialamide/or pargyline/or phenelzine/or pheniprazine/or tranylcypromine/ (2188)

174 antihypertensive drugs/or alpha methylparatyrosine/or captopril/or chlorpromazine/or clonidine/or guanethidine/ or hexamethonium/or hydralazine/or mecamylamine/or methyldopa/or phenoxybenzamine/or quinpirole/ (4387) 175 alpha blocker anti-hypertensive$.ti,ab. (0)

176 alpha blocker antihypertensive$.ti,ab. (0)

177 prazosin.ti,ab. (618)

178 Methylenedioxymethamphetamine/ (1923)

179 (mdma or ecstasy).ti,ab. (3061)

180 155 or 156 or 157 or 158 or 159 or 160 or 161 or 162 or 163 or 164 or 165 or 166 or 167 or 168 or 169 or 170 or 171 or 172 or 173 or 174 or 175 or 176 or 177 or 178 or 179 (99,763)

181 90 and 154 (2588)

182 90 and 180 (306)

183 181 or 182 (2861)

184 limit 183 to human (2798) 185 limit 184 to yr=“1992 -Current” (2658)

Science Citation Index via Web of Science

Search date: 20 April 2017.

Records retrieved: 1066.

Date range searched: 1900 onwards.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 155 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 22 Search strategy for Science Citation Index via Web of Science

#16 1066 #15 OR #11

Indexes=SCI-EXPANDED Timespan=1992-2017

#15 204 #14 AND #7

Indexes=SCI-EXPANDED Timespan=1992-2017

#14 352,711 #13 OR #12

Indexes=SCI-EXPANDED Timespan=1992-2017

#13 188,961 TS=((hypnotic or sedative) NEAR/1 (drug$ or agent$)) OR TS=(hypnotics or sedatives) OR TS=(alprazolam or amobarbital or azaperone or barbital or bromisovalum or “chloral hydrate” or chloralose or chlordiazepoxide or chlormethiazole or dexmedetomidine or diazepam or diphenhydramine or eszopiclone or ethchlorvynol or etomidate or etorphine or flurazepam or glutethimide or hexobarbital or lorazepam or medazepam or medetomidine or mephobarbital or meprobamate or methapyrilene or methaqualone or midazolam or nitrazepam or oxazepam or paraldehyde or pentobarbital or phenobarbital or propofol or secobarbital or temazepam or thiamylal or thiopental or xylazine) OR TS=(“z drug$”)ORTS=(“anti-anxiety agent$” or “anti-anxiety drug$”)ORTS=(“antianxiety agent$” or “antianxiety drug$”)ORTS=(“anti anxiety agent$” or “anti anxiety drug$”)ORTS=(“anxiolytic agent$” or “anxiolytic drug$” or anxiolytics) OR TS=(bromazepam or buspirone or chlormezanone or “clorazepate dipotassium” or estazolam or flunitrazepam or fluvoxamine or nordazepam or ondansetron or oxprenolol or prazepam or pregabalin or ritanserin or tranylcypromine or trazodone or triazolam or zolazepam or benzodiazepines or benzodiazepinones or “sedative antihistamine$” or promethazine) OR TS=(“antidepressive agent$” or “antidepressive drug$” or antidepressives) OR TS=(“anti-depressive agent$” or “anti-depressive drug$” or antidepressives) OR TS=(“anti depressive agent$” or “anti depressive drug$” or antidepressives) OR TS=(benactyzine or clorgyline or deanol or “desvenlafaxine succinate” or “duloxetine hydrochloride” or iproniazid or isocarboxazid or “lithium carbonate” or “lithium compounds” or moclobemide or nialamide or phenelzine or pizotyline or rolipram or sertraline or tranylcypromine or “vilazodone hydrochloride” or imipramine or mirtazapine) OR TS=(“antipsychotic agent$” or “antipsychotic drug$” or antipsychotics) OR TS=(“anti-psychotic agent$” or “anti-psychotic drug$” or anti-psychotics) OR TS=(“anti psychotic agent$” or “anti psychotic drug$” or anti psychotics) OR TS=(acepromazine or aripiprazole or azaperone or benperidol or butaclamol or chlorpromazine or chlorprothixene or clopenthixol or clozapine or droperidol or etazolate or flupenthixol or fluphenazine or fluspirilene or haloperidol or loxapine or lurasidone hydrochloride or mesoridazine or methiothepin or methotrimeprazine or molindone or ondansetron or “paliperidone palmitate” or penfluridol or perazine or perphenazine or pimozide or prochlorperazine or promazine or quetiapine fumarate or raclopride or remoxipride or reserpine or risperidone or ritanserin or spiperone or sulpiride or thioridazine or thiothixene or “tiapride hydrochloride” or trifluoperazine or trifluperidol or triflupromazine or olanzapine)

Indexes=SCI-EXPANDED Timespan=1992-2017 #12 202,663 TS=(“anticonvulsants agent$” or “anticonvulsant drug$” or anticonvulsants) OR TS=(“anti-convulsants agent$” or “anti-convulsant drug$” or anti-convulsants) OR TS=(“anti convulsants agent$” or “anti convulsant drug$” or anti convulsants) OR TS=(acetazolamide or bromides or carbamazepine or clonazepam or “clorazepate dipotassium” or diazepam or dimethadione or estazolam or ethosuximide or flunarizine or lorazepam or magnesium sulfate or medazepam or mephenytoin or mephobarbital or meprobamate or nitrazepam or paraldehyde or phenobarbital or phenytoin or pregabalin or primidone or riluzole or thiopental or tiletamine or trimethadione or “valproic acid” or vigabatrin) OR TS=(“antimanic agent$” or “antimanic drug$”)ORTS=(“anti-manic agent$” or “anti-manic drug$”) OR TS=(“anti manic agent$” or “anti manic drug$”)ORTS=(“lithium chloride” or “lithium compounds” or lamotrigine or topiramate) OR TS=(“monoamine oxidase inhibitors” or chlorphenamidine or clorgyline or cuprizone or furazolidone or harmaline or harmine or isocarboxazid or moclobemide or monocrotophos or pargyline or selegiline or tranylcypromine or Prazosin or “N-Methyl-3 4-methylenedioxyamphetamine” or MDMA or ecstasy)

Indexes=SCI-EXPANDED Timespan=1992-2017

#11 915 #10 AND #7

Indexes=SCI-EXPANDED Timespan=1992-2017

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TABLE 22 Search strategy for Science Citation Index via Web of Science (continued)

#10 130,643 #9 OR #8

Indexes=SCI-EXPANDED Timespan=1992-2017

#9 75,396 TS=(acceptance NEAR/2 therap$) OR TS=(commitment NEAR/2 therap$) OR TS=(hypnosis or hypnotherap$) OR TS=(mindfulness) OR TS=(“supportive therapy”)ORTS=(non-directive NEAR/1 (counselling or counseling)) OR TS=(nondirective NEAR/1 (counselling or counseling)) OR TS= (“non directive” NEAR/1 (counselling or counseling)) OR TS=(psychotherapy or “brief psychotherapy” or “group psychotherapy” or “psychodynamic psychotherapy”)ORTS=(“rational emotive psychotherapy”)ORTS=(“rational-emotive psychotherapy”)ORTS=(“psychodynamic therap$”) OR TS=(“inter personal psychotherap$” or “interpersonal psychotherap$” or “inter-personal psychotherap$”)ORTS=((compassion or schema or sensorimotor) NEAR/2 therap$) OR TS= (counseling or counselling) OR TS=(“accelerated resolution”)

Indexes=SCI-EXPANDED Timespan=1992-2017

#8 60,687 TS=(cognitive NEAR/3 (therap$ or treat$ or restructur$ or rescript$)) OR TS=(CBT or CPT or TFCBT) OR TS=(“trauma focus$ CBT”)ORTS=(behavior$ NEAR/2 (therap$ or treat$ or modif$)) OR TS=(behaviour$ NEAR/2 (therap$ or treat$ or modif$)) OR TS=(biofeedback or neurofeedback or “sensory feedback”)ORTS=(“implosive therapy”)ORTS=(“virtual reality therapy”)ORTS= (psychological NEAR/2 desensiti$) OR TS=(“eye movement desensitisation reprocessing” or “eye movement desensitization reprocessing”)ORTS=(EMDR) OR TS=(exposure NEAR/2 (imaginal or live or prolonged or therap$ or treat$)) OR TS=(“imaginal flooding”)ORTS=(“image habituation”)OR TS=(“inoculation training”)

Indexes=SCI-EXPANDED Timespan=1992-2017

#7 9164 #6 AND #5

Indexes=SCI-EXPANDED Timespan=1992-2017

#6 29,452 TOPIC: (“posttraumatic stress disorder*”) OR TOPIC: (“post-traumatic stress disorder*”) OR TOPIC: (“post traumatic stress disorder*”) OR TOPIC: (“posttraumatic stress*”) OR TOPIC: (“post-traumatic stress*”) OR TOPIC: (“post traumatic stress*”) OR TOPIC: (“traumatic stress*”) OR TOPIC: (posttrauma$ or post-trauma$ or “post trauma$”) OR TOPIC: (“combat stress” or “combat disorder”) OR TOPIC: (DESNOS) OR TOPIC: (“extreme distress”) OR TOPIC: (“complex trauma”) OR TOPIC: (complex NEAR/3 trauma) OR TOPIC: (traumatic NEAR/2 (stress or memor$)) OR TOPIC: (traumatization or traumatisation) OR TOPIC: (trauma$ NEAR/3 (expos$ or event$ or experienc$))

Indexes=SCI-EXPANDED Timespan=1992-2017

#5 288,605 #4 OR #3 OR #2 OR #1

Indexes=SCI-EXPANDED Timespan=1992-2017

#4 29,766 TOPIC: (victim$) OR TOPIC: (prisoner$) OR TOPIC: (soldier$ or veteran$) AND TOPIC: ((expose$ or exposure) NEAR/2 (abuse or assault$ or disaster$ or terror$ or torture$ or trauma$ or rape or violen$ or war or warfare)) AND TOPIC: (survivor$ NEAR/2 (abuse or assault$ or disaster$ or terror$ or torture$ or trauma$ or rape or violen$ or war or warfare)) AND TOPIC: (victim$ NEAR/2 (abuse or assault$ or crime or disaster$ or rape or terror$ or torture$ or trauma$ or violen$ or war or warfare)) AND TOPIC: (witness$ NEAR/2 (abuse or assault$ or disaster$ or rape or terror$ or torture$ or trauma$ or violen$ or war or warfare))

Indexes=SCI-EXPANDED Timespan=1992-2017

#3 202,637 TOPIC: (disaster$ or earthquake$ or tsunami$) OR TOPIC: (“natural disaster$”) OR TOPIC: (humanitarian NEAR/2 (crisis or crises)) OR TOPIC: (catastrophe$ or “catastrophic event$” or “catastrophic experience$”) OR TOPIC: (survivor*) OR TOPIC: (refugee$ or “asylum seeker$” or migrant$) OR TOPIC: ((forcibly or internally) NEAR/2 displace$) OR TOPIC: (displace$ NEAR/2 (people or person$ or civilian$))

Indexes=SCI-EXPANDED Timespan=1992-2017 continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 157 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1

TABLE 22 Search strategy for Science Citation Index via Web of Science (continued)

#2 25,515 TOPIC: (“human rights abuse*”) OR TOPIC: ((human or person or people) NEAR/2 (traffick$ or exploit$)) OR TOPIC: ((forced or exploit$) NEAR/2 labour) OR TOPIC: (“organ traffick$”) OR TOPIC: (slavery or “slave trade$” or enslave$) OR TOPIC: (torture$) OR TOPIC: (prostitution or “sex work$” or brothel$) OR TOPIC: (sex NEAR/2 (exploit$ or traffick$)) OR TOPIC: (terrorism or terrorist$ or “political terror$”) OR TOPIC: (warfare or “war crime$” or “armed conflict$” or “civil conflict” or “civil war$” or “civil unrest”) OR TOPIC: (“ethnic conflict$” or “ethnic unrest” or “ethnic cleans*” or genocide or holocaust) OR TOPIC: (persecution or victimization or victimisation) OR TOPIC: (imprison$ or “concentration camp”)

Indexes=SCI-EXPANDED Timespan=1992-2017 #1 47,352 TS=(violence) OR TS=(batter* NEAR/2 (wife$ or wive$ or woman or women or men or husband$ or partner$)) OR TS=(physical$ NEAR/2 (abus$ or assault$ or violen$ or aggress$)) OR TS=(emotional near/2 abus*) OR TS=(rape) OR TS=(sexual$ NEAR/2 (abus$ or assault$ or violen$ or aggress$)) OR TS=(child$ NEAR/2 (abus$ or exploit or maltreat$ or neglect$ or trauma$)) OR TS=(“non accidental injur$” or “non-accidental injur$” or “nonaccidental injur$”)

Indexes=SCI-EXPANDED Timespan=1992-2017

158

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Appendix 2 Literature search strategies for the qualitative acceptability review

he original searches were carried out in June 2017 using the following databases: CINAHL, TEMBASE, MEDLINE and PsycINFO. Results were restricted to 1992 onwards.

The numbers of records identified in each database are as follows: l CINAHL: 470 l EMBASE: 1749 l MEDLINE: 1151 l PsycINFO: 919.

The total number of records identified before de-duplication was 4289; after de-duplication, 3162 records were left.

This set was subsequently de-duplicated against the results of the effectiveness searches to leave a total of 1574 records.

CINAHL via EBSCOhost

Search date: 1 June 2017.

TABLE 23 Search strategy for CINAHL via EBSCOhost

Search terms Search options

S1 (MH “Stress Disorders, Post-Traumatic+”)

S2 TX (PTSD or CPTSD) OR TX posttrauma* OR TX post-trauma* OR TX “post trauma*” OR TX “post traumatic stress” OR TX “combat stress*” OR TX “combat disorder*” OR TX DESNOS OR TX “complex trauma*” OR TX “complex N3 trauma*” OR TX “traumatic stress” OR TX “traumatic memor*”

S3 TX traumatisation OR TX traumatization OR TX (trauma* N3 (expos* or event* or experienc*))

S4 S1 OR S2 OR S3

S5 (MH “Cognitive Therapy+”)ORTX“cognitive behaviour* therap*” OR TX “cognitive behavior* therap*” OR TX “cognitive restructuring” OR TX “cognitive rescripting” OR TX “cognitive processing therap*” OR TX (CPT or CBT or TFCBT) OR TX “cognitive therap*” OR TX “cognitive behavioural treat*” OR TX “cognitive behavioral treat*” OR TX “cognitive trauma therap*” OR TX “trauma focus* CBT”

S6 (MH “Behavior Therapy”) OR TX (behavior* N2 (therap* or treat* or modif*)) OR TX (behavior* N2 (therap* or treat* or modif*)) OR TX ((“dialectical behavio*”) N1 (therap* or treat*)) OR TX (biofeedback or neurofeedback or “sensory feedback”)ORTX psychological N2 desensiti#ation OR TX “eye movement desensiti#ation reprocessing” OR TX EMDR OR TX (exposure N1 (therap* or treat*)) OR TX “live exposure” OR TX “imaginal exposure” OR TX “prolonged exposure therapy” S7 TX “imaginal flooding” OR TX “exposure inhibition therap*” OR TX “implosive therap*” OR TX “image habituation” OR TX “inoculation training”

S8 ((MH “Acceptance and Commitment Therapy”)) OR TX acceptance N2 therap* OR TX commitment N2 therap* continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 159 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 2

TABLE 23 Search strategy for CINAHL via EBSCOhost (continued)

Search terms Search options

S9 (MH “Biofeedback”)

S10 (MH “Feedback”)

S11 (MH “Eye Movement Desensitization and Reprogramming”)

S12 (MH “Virtual Reality Exposure Therapy”)

S13 (MH “Hypnosis”)

S14 TX hypnosis or hypnotherap* S15 (MH “Mindfulness”)

S16 TX mindfulness

S17 TX “supportive therap*” OR TX (non-directive N1 (counselling or counseling)) OR TX (“non directive” N1 (counselling or counseling))

S18 ((MH “Psychotherapy”) OR (MH “Psychotherapy, Brief”) OR (MH “Psychotherapy, Group”) OR (MH “Psychotherapy, Psychodynamic”)) OR TX psychodynamic N1 therap* OR TX “inter personal psychotherap*” OR TX “interpersonal psychotherap*” OR TX IPT OR TX “compassion therap*” OR TX “accelerated resolution*” OR TX “sensorimotor therap*” OR TX “schema therap*” OR TX stress N2 manag*

S19 (MH “Counseling”)ORTX“non-directive counsel*” OR TX “non directive counsel*” OR TX “nondirective counsel*” OR “compassion therap*”

S20 S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19

S21 ((MH “Hypnotics and Sedatives”)) OR TX (alprazolam or amobarbital or azaperone or barbital or bromisovalum or “chloral hydrate” or chloralose or chlordiazepoxide or chlormethiazole or dexmedetomidine or diazepam or diphenhydramine or eszopiclone or ethchlorvynol or etomidate or etorphine or flurazepam or glutethimide or hexobarbital or lorazepam or medazepam or medetomidine or mephobarbital or meprobamate or methapyrilene or methaqualone or midazolam or nitrazepam or oxazepam or paraldehyde o...

S22 (MH “Antianxiety Agents+”) OR (bromazepam or buspirone or chlormezanone or “clorazepate dipotassium” or estazolam or flunitrazepam or fluvoxamine or nordazepam or ondansetron or oxprenolol or prazepam or pregabalin or ritanserin or tranylcypromine or trazodone or triazolam or zolazepam or benzodiazepines or benzodiazepinones or “sedative antihistamine*” or promethazine)

S23 (MH “Antidepressive Agents+”) OR TX (benactyzine or clorgyline or deanol or “desvenlafaxine succinate” or “duloxetine hydrochloride” or iproniazid or isocarboxazid or “lithium carbonate” or “lithium compounds” or moclobemide or nialamide or phenelzine or pizotyline or rolipram or sertraline or tranylcypromine or “vilazodone hydrochloride” or Imipramine or mirtazapine)

S24 (MH “Antipsychotic Agents+”) OR TX (acepromazine or aripiprazole or azaperone or benperidol or butaclamol or chlorpromazine or chlorprothixene or clopenthixol or clozapine or droperidol or etazolate or flupenthixol or fluphenazine or fluspirilene or haloperidol or loxapine or “lurasidone hydrochloride” or mesoridazine or methiothepin or methotrimeprazine or molindone or ondansetron or “paliperidone palmitate” or penfluridol or perazine or perphenazine or pimozide or prochlorperazine) OR TX (p...

S25 (MH “Anticonvulsants+”) OR TX (anticonvulsants or acetazolamide or bromides or carbamazepine or clonazepam or “clorazepate dipotassium” or diazepam or dimethadione or estazolam or ethosuximide or flunarizine or lorazepam or “magnesium sulfate” or medazepam or mephenytoin or mephobarbital or meprobamate or nitrazepam or paraldehyde or phenobarbital or phenytoin or pregabalin or primidone or riluzole or thiopental or tiletamine or trimethadione or “valproic acid” or vigabatrin)

S26 (MH “Antimanic Agents+”)ORTX(“lithium chloride” or “lithium compounds” or lamotrigine or topiramate)

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TABLE 23 Search strategy for CINAHL via EBSCOhost (continued)

Search terms Search options

S27 (MH “Monoamine Oxidase Inhibitors+”) OR TX (chlorphenamidine or clorgyline or cuprizone or furazolidone or harmaline or harmine or isocarboxazid or moclobemide or monocrotophos or pargyline or selegiline or tranylcypromine or Prazosin or N-Methyl-3, 4-methylenedioxyamphetamine or MDMA or ecstasy)

S28 S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27

S29 S4 AND S20 (3665)

S30 S4 AND S28 (820)

S31 S29 OR S30 (4259)

S32 (MH “Qualitative Studies”) (74,214)

S33 (MH “Interviews”) OR (MH “Unstructured Interview”) OR (MH “Semi-Structured (156,659) Interview”)

S34 (MH “Ethnographic Research”) (6044)

S35 (MH “Grounded Theory”) (11,936)

S36 (MH “Thematic Analysis”) (41,678) S37 (MH “Observational Methods”) OR (MH “Participant Observation”) (16,594)

S38 (MH “Field Notes”) (6623)

S39 (MH “Narratives”) (11,936)

S40 (MH “Field Studies”) (2485)

S41 (MH “Audiorecording”) (36,402)

S42 (MH “Focus Groups”) (31,284)

S43 (MH “Descriptive Research”) (60,598) S44 (MH “Case Studies”) (16,717)

S45 (MH “Discourse Analysis”) (3490) S46 (MH “Exploratory Research”) (29,405)

S47 (MH “Phenomenology”) (2577)

S48 (MH “Naturalistic Inquiry”) (929)

S49 (MH “Open-Ended Questionnaires”) (3206)

S50 (MH “Videorecording”) (22,181) S51 (MH “Anthropology, Cultural”) (1713)

S52 “conversation* analysis” OR “comparative method*” OR hermeneutic* OR participatory OR (45,445) in-depth OR key informant* OR narration*

S53 S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 (325,689) OR S43 OR S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR S51 OR S52

S54 S31 AND S53 (470)

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 161 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 2

EMBASE via Ovid

Search date: 1 June 2017.

Date range searched: 1980 to 2017 week 22.

TABLE 24 Search strategy for EMBASE via Ovid

1 Posttraumatic Stress Disorder/ (45,884) 2 (PTSD or CPTSD).ti,ab. (22,707) 3 posttrauma$.ti,ab. (34,058) 4 post-trauma$.ti,ab. (30,965) 5 “post trauma$”.ti,ab. (30,965) 6 post traumatic stress.ti,ab. (12,036) 7 post traumatic stress.kw. (2854) 8 combat stress$.ti,ab. (405) 9 combat disorder$.ti,ab. (18) 10 DESNOS.ti,ab. (39) 11 “Disorders of Extreme Distress Not Otherwise Specified”.ti,ab. (0) 12 complex trauma$.ti,ab. (454) 13 (complex adj3 trauma$).ti,ab. (1408) 14 traumatic stress.ti,ab. (14,416) 15 traumatic memor$.ti,ab. (768) 16 traumatization.ti,ab. (1152) 17 traumatisation.ti,ab. (242) 18 (trauma$ adj3 (expos$ or event$ or experienc$)).ti,ab. (20,405) 19 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 (95,383) 20 exp Cognitive Therapy/ (42,280) 21 cognitive behaviour$ therapy.ti,ab. (5626) 22 cognitive behavior$ therapy.ti,ab. (10,664) 23 cognitive restructuring.ti,ab. (1093) 24 cognitive rescripting.ti,ab. (0) 25 cognitive processing therapy.ti,ab. (197) 26 CPT.ti,ab. (15,122) 27 cognitive therapy.ti,ab. (3508) 28 cognitive behavioural treatment$.ti,ab. (571) 29 cognitive behavioral treatment$.ti,ab. (1879) 30 (CBT or TFCBT).ti,ab. (11,500) 31 cognitive trauma therapy.ti,ab. (7) 32 trauma focus$ CBT.ti,ab. (46) 33 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 (64,373) 34 exp Behavior Therapy/ (40,674) 35 (behavior$ adj2 (therap$ or treat$ or modif$)).ti,ab. (33,760)

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TABLE 24 Search strategy for EMBASE via Ovid (continued)

36 (behaviour$ adj2 (therap$ or treat$ or modif$)).ti,ab. (13,506) 37 (dialectical behavio$ adj (therap$ or treat$)).ti,ab. (811) 38 biofeedback, psychology/or feedback, sensory/or neurofeedback/ (20,411) 39 (biofeedback or neurofeedback or sensory feedback).ti,ab. (10,762) 40 eye movement desensitization reprocessing/or implosive therapy/or virtual reality exposure therapy/ (438) 41 (psychological adj2 desensiti$).ti,ab. (6) 42 eye movement desensiti?ation reprocessing.ti,ab. (38) 43 EMDR.ti,ab. (559) 44 (exposure adj (therap$ or treat$)).ti,ab. (2781) 45 live exposure.ti,ab. (16) 46 imaginal exposure.ti,ab. (180) 47 prolonged exposure therapy.ti,ab. (111) 48 imaginal flooding.ti,ab. (20) 49 exposure inhibition therap$.ti,ab. (0) 50 implosive therap$.ti,ab. (36) 51 image habituation.ti,ab. (4) 52 inoculation training.ti,ab. (115) 53 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 (102,846) 54 “Acceptance and Commitment Therapy”/ (709) 55 (acceptance adj2 therap$).ti,ab. (363) 56 (commitment adj2 therap$).ti,ab. (838) 57 Hypnosis/ (12,985) 58 (hypnosis or hypnotherap$).ti,ab. (8081) 59 Mindfulness/ (3457) 60 mindfulness.ti,ab. (5257) 61 supportive therap$.ti,ab. (5309) 62 (non-directive adj (counselling or counseling)).ti,ab. (114) 63 (nondirective adj (counselling or counseling)).ti,ab. (50) 64 (non directive adj (counselling or counseling)).ti,ab. (114) 65 Psychotherapy/or Group Therapy/or Psychodynamic Psychotherapy/ (93,420) 66 psychodynamic therap$.ti,ab. (627) 67 inter personal psychotherap$.ti,ab. (1) 68 interpersonal psychotherap$.ti,ab. (930) 69 IPT.ti,ab. (2387) 70 (compassion adj2 therap$).ti,ab. (62) 71 accelerated resolution.ti,ab. (112) 72 sensorimotor therap$.ti,ab. (22) 73 schema therapy.ti,ab. (174) 74 (stress adj2 manag$).ti,ab. (6583) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 163 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 2

TABLE 24 Search strategy for EMBASE via Ovid (continued)

75 supportive therap$.ti,ab. (5309) 76 Counseling/ (52,136) 77 (non-directive counsel$ or non directive counsel$ or nondirective counsel$).ti,ab. (165) 78 compassion therap$.ti,ab. (2) 79 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 or 62 or 63 or 64 or 65 or 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 or 75 or 76 or 77 or 78 (174,613) 80 33 or 53 or 79 (291,814) 81 19 and 80 (10,397) 82 hypnotic sedative agent/or alprazolam/or amobarbital/or azaperone/or barbital/or bromisovalum/or chloral hydrate/or chloralose/or chlordiazepoxide/or chlomethiazole/or dexmedetomidine/or diazepam/or diphenhydramine/or eszopiclone/or ethchlorvynol/or etomidate/or etorphine/or flurazepam/or glutethimide/or hexobarbital/or lorazepam/ or medazepam/or medetomidine/or methylphenobarbital/or meprobamate/or methapyrilene/or methaqualone/or midazolam/or nitrazepam/or oxazepam/or paraldehyde/or pentobarbital/or phenobarbital/or propofol/or secobarbital/ or temazepam/or thiamylal/or thiopental/or xylazine/ (276,213) 83 z drugs.ti,ab. (207) 84 anxiolytic agent/or bromazepam/or buspirone/or chlormezanone/or clorazepate dipotassium/or estazolam/or flunitrazepam/or fluvoxamine/or nordazepam/or ondansetron/or oxprenolol/or prazepam/or pregabalin/or ritanserin/or tranylcypromine/or trazodone/or triazolam/or zolazepam/ (91,974) 85 benzodiazepine derivative/ (36,147) 86 sedative antihistamine$.ti,ab. (115) 87 promethazine/ (11,286) 88 antidepressive agent/or benactyzine/or clorgyline/or deanol/or desvenlafaxine/or duloxetine/or iproniazid/or isocarboxazid/or lithium carbonate/or lithium derivative/or moclobemide/or nialamide/or phenelzine/or pizotifen/or rolipram/or sertraline/or tranylcypromine/or vilazodone/ (131,288) 89 Imipramine/ (29,724) 90 mirtazapine/ (10,727) 91 neuroleptic agent/or acepromazine/or aripiprazole/or azaperone/or benperidol/or butaclamol/or chlorpromazine/or chlorprothixene/or clopenthixol/or clozapine/or droperidol/or etazolate/or flupentixol/or fluphenazine/or fluspirilene/or haloperidol/or loxapine/or lurasidone/or mesoridazine/or metitepine/or methotrimeprazine/or molindone/or ondansetron/ or paliperidone/or penfluridol/or perazine/or perphenazine/or pimozide/or prochlorperazine/or promazine/or quetiapine/ or raclopride/or remoxipride/or reserpine/or risperidone/or ritanserin/or spiperone/or sulpiride/or thioridazine/or tiothixene/or tiapride/or trifluoperazine/or trifluperidol/or triflupromazine/ (221,511) 92 olanzapine/ (29,757) 93 anticonvulsive agent/or acetazolamide/or bromides/or carbamazepine/or clonazepam/or clorazepate dipotassium/ or diazepam/or dimethadione/or estazolam/or ethosuximide/or flunarizine/or lorazepam/or magnesium sulfate/or medazepam/or mephenytoin/or methylphenobarbital/or meprobamate/or nitrazepam/or paraldehyde/or phenobarbital/ or phenytoin/or pregabalin/or primidone/or riluzole/or thiopental/or tiletamine/or trimethadione/or valproic acid/or vigabatrin/ (323,161) 94 tranquilizer/or lithium chloride/or lithium derivative/ (21,662) 95 lamotrigine/ (21,528) 96 topiramate/ (18,511) 97 monoamine oxidase inhibitor/or chlorphenamidine/or clorgyline/or cuprizone/or furazolidone/or harmaline/or harmine/or isocarboxazid/or moclobemide/or monocrotophos/or pargyline/or selegiline/or tranylcypromine/(38,999) 98 Prazosin/ (21,809) 99 3,4 methylenedioxyamphetamine/ (1999) 100 (MDMA or ecstasy).ti,ab. (6408) 101 82 or 83 or 84 or 85 or 86 or 87 or 88 or 89 or 90 or 91 or 92 or 93 or 94 or 95 or 96 or 97 or 98 or 99 or 100 (796,293)

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TABLE 24 Search strategy for EMBASE via Ovid (continued)

102 19 and 101 (6845) 103 81 or 102 (15,327) 104 qualitative research/ (44,728) 105 unstructured interview/or semi structured interview/or interview/ (180,660) 106 ethnography/ (1859) 107 grounded theory/ (4097) 108 thematic analysis/ (6983) 109 observational method/ (1260) 110 participant observation/ (4400) 111 narrative/ (5915) 112 field study/ (2893) 113 audio recording/ (1997) 114 descriptive research/ (14,116) 115 discourse analysis/ (760) 116 hermeneutics/ (167) 117 naturalistic inquiry/ (459) 118 phenomenology/ (8633) 119 participatory research/ (3550) 120 recording/ (41,930) 121 cultural anthropology/ (48,605) 122 case stud$.ti,ab. (92,088) 123 comparative method$.ti,ab. (2818) 124 field notes.ti,ab. (1743) 125 focus group$.ti,ab. (39,224) 126 conversation$ analysis.ti,ab. (506) 127 exploratory stud$.ti,ab. (13,200) 128 open-ended.ti,ab. (12,795) 129 in-depth.ti,ab. (55,739) 130 key informant$.ti,ab. (5832) 131 narration.ti,ab. (644) 132 104 or 105 or 106 or 107 or 108 or 109 or 110 or 111 or 112 or 113 or 114 or 115 or 116 or 117 or 118 or 119 or 120 or 121 or 122 or 123 or 124 or 125 or 126 or 127 or 128 or 129 or 130 or 131 (505,231) 133 103 and 132 (1259) 134 (accept$ or adherence or attitude$ or belief$ or believ$ or choice$ or choos$ or drop out$ or experienc$ or feasib$ or opinion$ or perceiv$ or percept$ or prefer$ or uptake or view$ or withdraw$).ti. (761,456) 135 103 and 134 (637) 136 133 or 135 (1799) 137 limit 136 to yr=“1992 -Current” (1749)

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 165 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 2

MEDLINE via Ovid

Search date: 1 June 2017.

Database: Ovid MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE.

Date range searched: 1946 to present.

TABLE 25 Search strategy for MEDLINE via Ovid

1 Stress Disorders, Post Traumatic/ (27,020) 2 (PTSD or CPTSD).ti,ab. (18,404)

3 posttrauma$.ti,ab. (30,457)

4 post-trauma$.ti,ab. (25,925)

5 “post trauma$”.ti,ab. (25,925)

6 post traumatic stress.ti,ab. (9454)

7 post traumatic stress.kw. (96)

8 combat stress$.ti,ab. (348) 9 combat disorder$.ti,ab. (15)

10 DESNOS.ti,ab. (30)

11 “Disorders of Extreme Distress Not Otherwise Specified”.ti,ab. (0)

12 complex trauma$.ti,ab. (409)

13 (complex adj3 trauma$).ti,ab. (1224)

14 traumatic stress.ti,ab. (10,931)

15 traumatic memor$.ti,ab. (594) 16 traumatization.ti,ab. (1004)

17 traumatisation.ti,ab. (192)

18 (trauma$ adj3 (expos$ or event$ or experienc$)).ti,ab. (16,547)

19 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 (75,969)

20 exp Cognitive Therapy/ (22,774)

21 cognitive behaviour$ therapy.ti,ab. (4058)

22 cognitive behavior$ therapy.ti,ab. (8246) 23 cognitive restructuring.ti,ab. (728)

24 cognitive rescripting.ti,ab. (0)

25 cognitive processing therapy.ti,ab. (181)

26 CPT.ti,ab. (10,875)

27 cognitive therapy.ti,ab. (2427)

28 cognitive behavioural treatment$.ti,ab. (408)

29 cognitive behavioral treatment$.ti,ab. (1406) 30 (CBT or TFCBT).ti,ab. (8178)

31 cognitive trauma therapy.ti,ab. (6)

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TABLE 25 Search strategy for MEDLINE via Ovid (continued)

32 trauma focus$ CBT.ti,ab. (31) 33 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 (41,296)

34 exp Behavior Therapy/ (65,175)

35 (behavior$ adj2 (therap$ or treat$ or modif$)).ti,ab. (27,210)

36 (behaviour$ adj2 (therap$ or treat$ or modif$)).ti,ab. (9995)

37 (dialectical behavio$ adj (therap$ or treat$)).ti,ab. (587)

38 biofeedback, psychology/or feedback, sensory/or neurofeedback/ (9410)

39 (biofeedback or neurofeedback or sensory feedback).ti,ab. (8547) 40 eye movement desensitization reprocessing/or implosive therapy/or virtual reality exposure therapy/ (1375)

41 (psychological adj2 desensiti$).ti,ab. (4)

42 eye movement desensiti?ation reprocessing.ti,ab. (25)

43 EMDR.ti,ab. (376)

44 (exposure adj (therap$ or treat$)).ti,ab. (2318)

45 live exposure.ti,ab. (11)

46 imaginal exposure.ti,ab. (149) 47 prolonged exposure therapy.ti,ab. (101)

48 imaginal flooding.ti,ab. (13)

49 exposure inhibition therap$.ti,ab. (0)

50 implosive therap$.ti,ab. (43)

51 image habituation.ti,ab. (3)

52 inoculation training.ti,ab. (79)

53 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 (91,074)

54 “Acceptance and Commitment Therapy”/ (187) 55 (acceptance adj2 therap$).ti,ab. (262)

56 (commitment adj2 therap$).ti,ab. (615)

57 Hypnosis/ (8767)

58 (hypnosis or hypnotherap$).ti,ab. (7616)

59 Mindfulness/ (1406)

60 mindfulness.ti,ab. (4162)

61 supportive therap$.ti,ab. (3938) 62 (non-directive adj (counselling or counseling)).ti,ab. (100)

63 (nondirective adj (counselling or counseling)).ti,ab. (54)

64 (non directive adj (counselling or counseling)).ti,ab. (100)

65 Psychotherapy/or Psychotherapy, Brief/or Psychotherapy, Group/or Psychotherapy, Multiple/or Psychotherapy, Psychodynamic/or Psychotherapy, Rational-emotive/ (66,081)

66 psychodynamic therap$.ti,ab. (435)

67 inter personal psychotherap$.ti,ab. (1)

68 interpersonal psychotherap$.ti,ab. (788)

69 IPT.ti,ab. (1934) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 167 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 2

TABLE 25 Search strategy for MEDLINE via Ovid (continued)

70 (compassion adj2 therap$).ti,ab. (41) 71 accelerated resolution.ti,ab. (86)

72 sensorimotor therap$.ti,ab. (22)

73 schema therapy.ti,ab. (113)

74 (stress adj2 manag$).ti,ab. (5239)

75 supportive therap$.ti,ab. (3938)

76 Counseling/ (33,064)

77 (non-directive counsel$ or non directive counsel$ or nondirective counsel$).ti,ab. (155) 78 compassion therap$.ti,ab. (1)

79 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 or 62 or 63 or 64 or 65 or 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 or 75 or 76 or 77 or 78 (122,833)

80 33 or 53 or 79 (212,817) 81 “hypnotics and sedatives”/or alprazolam/or amobarbital/or azaperone/or barbital/or bromisovalum/or chloral hydrate/or chloralose/or chlordiazepoxide/or chlormethiazole/or dexmedetomidine/or diazepam/or diphenhydramine/ or eszopiclone/or ethchlorvynol/or etomidate/or etorphine/or flurazepam/or glutethimide/or hexobarbital/or lorazepam/or medazepam/or medetomidine/or mephobarbital/or meprobamate/or methapyrilene/or methaqualone/or midazolam/or nitrazepam/or oxazepam/or paraldehyde/or pentobarbital/or phenobarbital/or propofol/or secobarbital/ or temazepam/or thiamylal/or thiopental/or xylazine/ (115,279)

82 z drugs.ti,ab. (129)

83 anti-anxiety agents/or bromazepam/or buspirone/or chlormezanone/or clorazepate dipotassium/or estazolam/or flunitrazepam/or fluvoxamine/or nordazepam/or ondansetron/or oxprenolol/or prazepam/or pregabalin/or ritanserin/or tranylcypromine/or trazodone/or triazolam/or zolazepam/ (33,247)

84 benzodiazepines/or benzodiazepinones/ (23,792)

85 sedative antihistamine$.ti,ab. (61) 86 promethazine.ti,ab. (2067)

87 antidepressive agents/or benactyzine/or clorgyline/or deanol/or desvenlafaxine succinate/or duloxetine hydrochloride/or iproniazid/or isocarboxazid/or lithium carbonate/or lithium compounds/or moclobemide/or nialamide/ or phenelzine/or pizotyline/or rolipram/or sertraline/or tranylcypromine/or vilazodone hydrochloride/ (55,863)

88 Imipramine/ (9836)

89 mirtazapine.ti,ab. (1789)

90 antipsychotic agents/or acepromazine/or aripiprazole/or azaperone/or benperidol/or butaclamol/or chlorpromazine/ or chlorprothixene/or clopenthixol/or clozapine/or droperidol/or etazolate/or flupenthixol/or fluphenazine/or fluspirilene/ or haloperidol/or loxapine/or lurasidone hydrochloride/or mesoridazine/or methiothepin/or methotrimeprazine/or molindone/or ondansetron/or paliperidone palmitate/or penfluridol/or perazine/or perphenazine/or pimozide/or prochlorperazine/or promazine/or quetiapine fumarate/or raclopride/or remoxipride/or reserpine/or risperidone/or ritanserin/or spiperone/or sulpiride/or thioridazine/or thiothixene/or tiapride hydrochloride/or trifluoperazine/or trifluperidol/or triflupromazine/ (115,485)

91 olanzapine.ti,ab. (7626)

92 anticonvulsants/or acetazolamide/or bromides/or carbamazepine/or clonazepam/or clorazepate dipotassium/ or diazepam/or dimethadione/or estazolam/or ethosuximide/or flunarizine/or lorazepam/or magnesium sulfate/or medazepam/or mephenytoin/or mephobarbital/or meprobamate/or nitrazepam/or paraldehyde/or phenobarbital/or phenytoin/or pregabalin/or primidone/or riluzole/or thiopental/or tiletamine/or trimethadione/or valproic acid/or vigabatrin/ (130,525)

93 antimanic agents/or lithium chloride/or lithium compounds/ (9289)

94 lamotrigine.ti,ab. (4677)

95 topiramate.ti,ab. (4081)

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TABLE 25 Search strategy for MEDLINE via Ovid (continued)

96 monoamine oxidase inhibitors/or chlorphenamidine/or clorgyline/or cuprizone/or furazolidone/or harmaline/or harmine/or isocarboxazid/or moclobemide/or monocrotophos/or pargyline/or selegiline/or tranylcypromine/ (18,012)

97 Prazosin/ (7586)

98 N-Methyl-3,4-methylenedioxyamphetamine/ (3654)

99 (MDMA or ecstasy).ti,ab. (5261) 100 81or82or83or84or85or86or87or88or89or90or91or92or93or94or95or96or97or98or99(409,556)

101 19 and 80 (5684)

102 19 and 100 (1860)

103 101 or 102 (7197)

104 Qualitative Research/ (34,279)

105 interview/ (27,920)

106 Grounded Theory/ (570) 107 Personal Narratives/ (2920)

108 Focus Groups/ (23,242)

109 Hermeneutics/ (122)

110 Anthropology, Cultural/ (5645)

111 interview$.ti,ab. (295,531)

112 ethnog$.ti,ab. (8787)

113 case stud$.ti,ab. (75,187) 114 grounded theory.ti,ab. (9150)

115 thematic analysis.ti,ab. (9942)

116 observational method$.ti,ab. (584)

117 comparative method$.ti,ab. (2606)

118 field notes.ti,ab. (1605)

119 participant observation.ti,ab. (2952)

120 narrative$.ti,ab. (26,469) 121 field stud$.ti,ab. (12,896)

122 audio recording.ti,ab. (240)

123 focus group$.ti,ab. (34,349)

124 conversation$ analysis.ti,ab. (454)

125 descriptive stud$.ti,ab. (22,097)

126 discourse analysis.ti,ab. (1338)

127 exploratory stud$.ti,ab. (11,645) 128 Hermeneutic.ti,ab. (2283)

129 naturalistic.ti,ab. (8879)

130 Phenomenolog$.ti,ab. (21,696)

131 Participatory.ti,ab. (9369)

132 Open-ended.ti,ab. (10,984)

133 in-depth.ti,ab. (49,756) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 169 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 2

TABLE 25 Search strategy for MEDLINE via Ovid (continued)

134 semi-structured.ti,ab. (29,761) 135 key informant$.ti,ab. (5436)

136 tape record$.ti,ab. (3069)

137 narration.ti,ab. (467)

138 104 or 105 or 106 or 107 or 108 or 109 or 110 or 111 or 112 or 113 or 114 or 115 or 116 or 117 or 118 or 119 or 120 or 121 or 122 or 123 or 124 or 125 or 126 or 127 or 128 or 129 or 130 or 131 or 132 or 133 or 134 or 135 or 136 or 137 (546,383)

139 103 and 138 (951)

140 (accept$ or adherence or attitude$ or belief$ or believ$ or choice$ or choos$ or drop out$ or experienc$ or feasib$ or opinion$ or perceiv$ or percept$ or prefer$ or uptake or view$ or withdraw$).ti. (680,726)

141 103 and 140 (344)

142 139 or 141 (1212) 143 limit 142 to yr=“1992 -Current” (1151)

PsycINFO via Ovid

Search date: 1 June 2017.

Date range searched: 1987 to May Week 4 2017.

TABLE 26 Search strategy for PsycINFO via Ovid

1 exp Posttraumatic Stress Disorder/ (26,903)

2 Complex PTSD/ (130)

3 DESNOS/ (15)

4 “Disorders of Extreme Distress Not Otherwise Specified”.ti,ab. (0)

5 (PTSD or CPTSD).ti,ab. (25,512)

6 posttrauma$.ti,ab. (26,670)

7 post-trauma$.ti,ab. (11,375) 8 “post trauma$”.ti,ab. (11,375)

9 post traumatic stress.ti,ab. (8922)

10 post traumatic stress.id. (2822)

11 combat stress$.ti,ab. (450)

12 combat disorder$.ti,ab. (12)

13 DESNOS.ti,ab. (54)

14 complex trauma$.ti,ab. (527)

15 (complex adj2 trauma$).ti,ab. (699) 16 traumatic stress.ti,ab. (11,652)

17 traumatic memor$.ti,ab. (1271)

18 traumatization.ti,ab. (1431)

19 traumatisation.ti,ab. (155)

170

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TABLE 26 Search strategy for PsycINFO via Ovid (continued)

20 (trauma adj2 (expos$ or event$ or experienc$)).ti,ab. (6690) 21 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 (46,932)

22 exp Cognitive Therapy/ (11,610)

23 cognitive behaviour$ therapy.ti,ab. (3892)

24 cognitive behavior$ therapy.ti,ab. (12,974)

25 cognitive restructuring.ti,ab. (1765)

26 cognitive rescripting.ti,ab. (0)

27 cognitive processing therapy.ti,ab. (277) 28 CPT.ti,ab. (1871)

29 cognitive therapy.ti,ab. (5079)

30 cognitive behavioural treatment$.ti,ab. (521)

31 cognitive behavioral treatment$.ti,ab. (2909)

32 (CBT or TFCBT).ti,ab. (10,696)

33 cognitive trauma therapy.ti,ab. (8)

34 trauma focus$ CBT.ti,ab. (57) 35 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 (32,467)

36 exp Behavior Therapy/ (11,576)

37 (behavior$ adj2 (therap$ or treat$ or modif$)).ti,ab. (33,755)

38 (behaviour$ adj2 (therap$ or treat$ or modif$)).ti,ab. (6941)

39 (dialectical behavio$ therap$ or dialectical behavio$ treat$).ti,ab. (1477)

40 DBT.ti,ab. (1136)

41 biofeedback, psychology/or feedback, sensory/or neurofeedback/ (1224)

42 (biofeedback or neurofeedback or sensory feedback).ti,ab. (4469) 43 desensitization, psychologic/or eye movement desensitization reprocessing/or implosive therapy/or virtual reality exposure therapy/ (152)

44 (psychological adj2 desensiti$).ti,ab. (3) 45 Eye Movement Desensitization Therapy/ (1241)

46 eye movement desensiti?ation reprocessing.ti,ab. (61)

47 EMDR.ti,ab. (1367)

48 Exposure Therapy/ (1988)

49 (exposure adj (therap$ or treat$)).ti,ab. (2129)

50 prolonged exposure therap$.ti,ab. (153)

51 live exposure.ti,ab. (21) 52 imaginal exposure.ti,ab. (267)

53 imaginal flooding.ti,ab. (21)

54 exposure inhibition therap$.ti,ab. (1)

55 implosive therap$.ti,ab. (29)

56 image habituation.ti,ab. (5)

57 inoculation training.ti,ab. (226) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 171 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 2

TABLE 26 Search strategy for PsycINFO via Ovid (continued)

58 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55 or 56 or 57 (51,566)

59 (acceptance adj2 therap$).ti,ab. (347)

60 (commitment adj2 therap$).ti,ab. (1499)

61 Hypnosis/(3983) 62 (hypnosis or hypnotherap$).ti,ab. (6655)

63 Mindfulness/ (6716)

64 mindfulness.ti,ab. (8233)

65 (supportive adj (therap$ or psychotherap$)).ti,ab. (1186)

66 (non-directive adj (counselling or counseling)).ti,ab. (40)

67 (nondirective adj (counselling or counseling)).ti,ab. (52)

68 (non directive adj (counselling or counseling)).ti,ab. (40) 69 psychodynamic therap$.ti,ab. (1267)

70 inter personal psychotherap$.ti,ab. (1)

71 interpersonal psychotherap$.ti,ab. (1175)

72 interpersonal therapy.ti,ab. (502)

73 IPT.ti,ab. (963)

74 (compassion adj2 therap$).ti,ab. (107)

75 accelerated resolution.ti,ab. (9) 76 sensorimotor therap$.ti,ab. (9)

77 schema therapy.ti,ab. (321)

78 Stress Management/ (4239)

79 Supportive Psychotherapy/ (461)

80 Group Psychotherapy/ (12,925)

81 Counseling/ (15,966)

82 (non-directive counsel$ or non directive counsel$ or nondirective counsel$).ti,ab. (92) 83 compassion therap$.ti,ab. (4)

84 59 or 60 or 61 or 62 or 63 or 64 or 65 or 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 or 75 or 76 or 77 or 78 or 79 or 80 or 81 or 82 or 83 (53,717)

85 35 or 58 or 84 (108,582) 86 21 and 85 (5589)

87 hypnotic drugs/or amobarbital/or apomorphine/or barbital/or chloral hydrate/or codeine/or flurazepam/or glutethimide/or hexobarbital/or meprobamate/or methaqualone/or nitrazepam/or pentobarbital/or phenobarbital/or secobarbital/or thalidomide/or thiopental/or triazolam/ (3430)

88 hypnotics.ti,ab. (1260)

89 hypnotic drug$.ti,ab. (286)

90 z drug$.ti,ab. (44)

91 tranquilizing drugs/or amitriptyline/or benactyzine/or doxepin/or haloperidol/or meprobamate/or minor tranquilizers/or neuroleptic drugs/or phenothiazine derivatives/or pimozide/or thiothixene/ (21,857)

92 exp benzodiazepines/ (7742)

93 sedative antihistamine$.ti,ab. (13)

172

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TABLE 26 Search strategy for PsycINFO via Ovid (continued)

94 promethazine.ti,ab. (125) 95 antidepressant drugs/or bupropion/or citalopram/or fluoxetine/or fluvoxamine/or iproniazid/or isocarboxazid/or lithium carbonate/or methylphenidate/or mianserin/or moclobemide/or molindone/or nefazodone/or nialamide/or nomifensine/or paroxetine/or phenelzine/or pheniprazine/or pipradrol/or serotonin norepinephrine reuptake inhibitors/ or sertraline/or sulpiride/or tranylcypromine/or trazodone/or tricyclic antidepressant drugs/or venlafaxine/or zimeldine/ (28,111)

96 Imipramine.ti,ab. (2559)

97 mirtazapine.ti,ab. (1118)

98 neuroleptic drugs/or aripiprazole/or clozapine/or molindone/or nialamide/or olanzapine/or quetiapine/or reserpine/or risperidone/or spiroperidol/or sulpiride/or tetrabenazine/ (25,765)

99 mood stabilizers/or anticonvulsive drugs/or carbamazepine/or lithium/or valproic acid/ (11,793)

100 mood stabilisers.ti,ab. (144)

101 antiepileptics.ti,ab. (281) 102 lamotrigine.ti,ab. (1802)

103 topiramate.ti,ab. (1501)

104 valproate.ti,ab. (2716)

105 monoamine oxidase inhibitors/or iproniazid/or isocarboxazid/or moclobemide/or nialamide/or pargyline/or phenelzine/or pheniprazine/or tranylcypromine/ (1627)

106 antihypertensive drugs/or alpha methylparatyrosine/or captopril/or chlorpromazine/or clonidine/or guanethidine/ or hexamethonium/or hydralazine/or mecamylamine/or methyldopa/or phenoxybenzamine/or quinpirole/ (2481) 107 alpha blocker anti-hypertensive$.ti,ab. (0)

108 alpha blocker antihypertensive$.ti,ab. (0)

109 prazosin.ti,ab. (579)

110 Methylenedioxymethamphetamine/ (1926)

111 (mdma or ecstasy).ti,ab. (2879)

112 87 or 88 or 89 or 90 or 91 or 92 or 93 or 94 or 95 or 96 or 97 or 98 or 99 or 100 or 101 or 102 or 103 or 104 or 105 or 106 or 107 or 108 or 109 or 110 or 111 (83,790)

113 21 and 112 (1054)

114 86 or 113 (6545)

115 Qualitative Research/ (7366)

116 exp INTERVIEWS/ (9209) 117 exp ETHNOGRAPHY/ (7251)

118 exp Grounded Theory/ (3212)

119 exp Observation Methods/ (3079)

120 exp NARRATIVES/ (16,768)

121 exp Audiotapes/ (250)

122 exp Discourse Analysis/ (7393)

123 conversation/ (7816)

124 exp HERMENEUTICS/ (1857) 125 exp PHENOMENOLOGY/ (10,792)

126 exp Participation/ (11,842)

127 exp Informants/ (734) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 173 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 2

TABLE 26 Search strategy for PsycINFO via Ovid (continued)

128 anthropology/ (4659) 129 case stud$.ti,ab. (74,204)

130 thematic analysis.ti,ab. (7137)

131 comparative method$.ti,ab. (1958)

132 field notes.ti,ab. (3029)

133 audio recording.ti,ab. (214)

134 focus group$.ti,ab. (27,182)

135 conversation$ analysis.ti,ab. (1659) 136 descriptive study.ti,ab. (5331)

137 exploratory stud$.ti,ab. (12,989)

138 naturalistic.ti,ab. (11,518)

139 (open-ended or in-depth).ti,ab. (52,099)

140 semi-structured.ti,ab. (26,340)

141 key informant$.ti,ab. (2662)

142 tape record$.ti,ab. (1949) 143 narration.ti,ab. (1417)

144 115 or 116 or 117 or 118 or 119 or 120 or 121 or 122 or 123 or 124 or 125 or 126 or 127 or 128 or 129 or 130 or 131 or 132 or 133 or 134 or 135 or 136 or 137 or 138 or 139 or 140 or 141 or 142 or 143 (271,473)

145 114 and 144 (652) 146 (accept$ or adherence or attitude$ or belief$ or believ$ or choice$ or choos$ or drop out$ or experienc$ or feasib$ or opinion$ or perceiv$ or percept$ or prefer$ or uptake or view$ or withdraw$).ti. (288,349)

147 114 and 146 (346)

148 145 or 147 (947) 149 limit 148 to yr=“1992 -Current” (919)

174

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Appendix 3 List of studies excluded, with reasons

TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion

Authors (year) Reason for exclusion

Abramowitz et al. (2008)188 Intervention did not meet criteria

Acierno et al. (2016)189 Intervention did not meet criteria

Aderka et al. (2013)190 Population did not meet criteria

Adler et al. (2009)191 Intervention did not meet criteria

Alderman et al. (2009)192 Study design did not meet criteria

Alderman et al. (2009)193 Study design did not meet criteria

Allan et al. (2015)194 Study design did not meet criteria

Allon (2015)195 Population did not meet criteria

Alvarez et al. (2011)196 Study design did not meet criteria

Amin et al. (2013)197 Article is a conference abstract

Angelo et al. (2008)198 Study design did not meet criteria

Arntz et al. (2007)199 Population did not meet criteria

Ayoughi et al. (2012)200 Study design did not meet criteria

Baños et al. (2011)201 Population did not meet criteria

Basharpoor et al. (2011)202 Population did not meet criteria

Bass et al. (2013)203 Population did not meet criteria

Batka et al. (2016)204 Intervention did not meet criteria

Benedek (2011)205 Study design did not meet criteria

Bensimon et al. (2012)206 Intervention did not meet criteria

Betancourt et al. (2014)207 Population did not meet criteria

Bisson (2003)208 Study design did not meet criteria

Bisson (2007)209 Population did not meet criteria

Blevins et al. (2011)210 Intervention did not meet criteria

Bohus et al. (2013)211 Population did not meet criteria

Bolton et al. (2014)212 Population did not meet criteria

Bomyea et al. (2015)213 Population did not meet criteria

Bormann et al. (2008)214 Intervention did not meet criteria

Bormann et al. (2013)215 Intervention did not meet criteria

Bormann et al. (2014)216 Article is a conference abstract

Bradley and Follingstad (2003)217 Population did not meet criteria

Brady et al. (2000)218 Population did not meet criteria

Bremner et al. (2004)219 Study design did not meet criteria continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 175 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 3

TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion (continued)

Authors (year) Reason for exclusion

Bremner et al. (2011)220 Article is a conference abstract

Brown et al. (2014)221 Intervention did not meet criteria

Bryan et al. (2016)222 Study design did not meet criteria

Bui et al. (2016)223 Article is a conference abstract

Byers et al. (2010)224 Study design did not meet criteria

Byers (2010)225 Study design did not meet criteria

Campbell et al. (2016)226 Intervention did not meet criteria

Carlson et al. (1998)157 Duplicate article

Carr et al. (2012)227 Intervention did not meet criteria

Castillo et al. (2016)228 Population did not meet criteria

Cates et al. (2004)229 Study design did not meet criteria

Celik et al. (2011)65 Duplicate article

Chemtob et al. (1997)230 Population did not meet criteria

Chen et al. (2013)231 Outcomes did not meet criteria

Chesney et al. (2014)232 Article is a conference abstract

Church et al. (2013)233 Intervention did not meet criteria

Church (2014)234 Study design did not meet criteria

Clark et al. (1999)235 Study design did not meet criteria

Classen et al. (2011)236 Population did not meet criteria

Cloitre and Koenen (2001)237 Study design did not meet criteria

Cole et al. (2007)238 Population did not meet criteria

Connolly and Sakai (2011)239 Intervention did not meet criteria

Cort et al. (2014)240 Study design did not meet criteria

Coulter (2010)241 Intervention did not meet criteria

Crespo and Arinero (2010)242 Population did not meet criteria

David et al. (2006)243 Study design did not meet criteria

Davidson et al. (1993)244 Study design did not meet criteria

Davidson et al. (2001)245 Population did not meet criteria

Davidson et al. (2001)246 Population did not meet criteria

Davis et al. (2000)247 Study design did not meet criteria

Davis et al. (2004)73 Duplicate article

Davis et al. (2008)72 Duplicate article

Davis et al. (2011)248 Population did not meet criteria

Dawson et al. (2016)249 Population did not meet criteria

Dempsey et al. (2014)233 Article is a conference abstract

Dieperink et al. (2008)250 Intervention did not meet criteria

Difede et al. (2014)251 Population did not meet criteria

Dorrepaal et al. (2012)252 Population did not meet criteria

176

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TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion (continued)

Authors (year) Reason for exclusion

Dorrepaal et al. (2013)253 Outcomes did not meet criteria

Doruk et al. (1999)254 Non-English language article

Dougherty (2002)255 Population did not meet criteria

Drozdek (1997)256 Study design did not meet criteria

Droždek and Bolwerk (2010)257 Intervention did not meet criteria

Drožđek et al. (2012)258 Intervention did not meet criteria

Duffy and Malloy (1994)259 Study design did not meet criteria

Duffy et al. (2007)260 Population did not meet criteria

Dunn et al. (2007)261 Population did not meet criteria

Durham et al. (2005)262 Study design did not meet criteria

Echeburúa et al. (1997)263 Population did not meet criteria

Echeburúa et al. (2014)264 Comparator did not meet criteria

Edmond et al. (2004)265 Outcomes did not meet criteria

Ekstrom et al. (2016)266 Article is a conference abstract

Ekstrom et al. (2016)267 Article is a conference abstract

Elkjaer et al. (2012)268 Article is a conference abstract

Ertl et al. (2011)269 Population did not meet criteria

Esala et al. (2017)270 Intervention did not meet criteria

Falsetti et al. (2003)271 Population did not meet criteria

Farchi and Gidron (2010)272 Intervention did not meet criteria

Fiorillo et al. (2017)273 Study design did not meet criteria

Foa et al. (1991)274 Population did not meet criteria

Foa et al. (1999)275 Population did not meet criteria

Foa et al. (2005)276 Population did not meet criteria

Forbes et al. (2001)277 Study design did not meet criteria

Forbes et al. (2008)278 Population did not meet criteria

Forbes et al. (2012)279 Population did not meet criteria

Ford et al. (2011)280 Population did not meet criteria

Fortney et al. (2015)281 Intervention did not meet criteria

Fortney et al. (2015)282 Intervention did not meet criteria

Frommberger et al. (2004)283 Population did not meet criteria

Galovski et al. (2009)284 Study design did not meet criteria

Galovski et al. (2012)285 Population did not meet criteria

Gamito et al. (2009)286 Study design did not meet criteria

Garfield et al. (2001)287 Study design did not meet criteria

Gatz et al. (2007)288 Population did not meet criteria

Gebler and Maercker (2007)289 Non-English language article continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 177 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 3

TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion (continued)

Authors (year) Reason for exclusion

Gelpin et al. (1996)290 Population did not meet criteria

Gillin et al. (2001)291 Study design did not meet criteria

Ginsberg (2003)292 Study design did not meet criteria

Ginzburg et al. (2009)293 Outcomes did not meet criteria

Glover (1993)294 Study design did not meet criteria

Glynn et al. (1999)295 Intervention did not meet criteria

Goldberg et al. (2003)296 Study design did not meet criteria

Gosselin et al. (2016)297 Article is a conference abstract

Graham-Bermann and Miller (2013)298 Intervention did not meet criteria

Gray et al. (2012)299 Study design did not meet criteria

Gros et al. (2011)300 Comparator did not meet criteria

Gros et al. (2011)301 Comparator did not meet criteria

Gutner et al. (2013)302 Population did not meet criteria

Hall et al. (2014)303 Outcomes did not meet criteria

Hamner (1996)304 Article is a letter to the editor

Hamner et al. (2003)305 Study design did not meet criteria

Harris et al. (2011)306 Intervention did not meet criteria

Haynes et al. (2012)307 Article is a conference abstract

Hébert and Bergeron (2007)308 Population did not meet criteria

Held and Owens (2015)309 Population did not meet criteria

Hensel-Dittmann et al. (2011)310 Population did not meet criteria

Hertzberg et al. (2000)311 Population did not meet criteria

Hertzberg et al. (2002)312 Study design did not meet criteria

Hijazi et al. (2013)313 Article is a conference abstract

Hobfoll et al. (2016)314 Population did not meet criteria

Holliday et al. (2015)315 Population did not meet criteria

Hopton and Huta (2013)316 Population did not meet criteria

Hughes and Rasmussen (2010)162 Study design did not meet criteria

Igreja et al. (2004)317 Intervention did not meet criteria

Ironson et al. (2002)318 Population did not meet criteria

Ivarsson et al. (2014)319 Population did not meet criteria

Iverson et al. (2011)320 Outcomes did not meet criteria

Jaberghaderi et al. (2002)321 Population did not meet criteria

Jain et al. (2012)322 Intervention did not meet criteria

Jenkins et al. (2014)323 Article is a conference abstract

Jerud et al. (2014)324 Population did not meet criteria

Jetly et al. (2015)325 Study design did not meet criteria

Johnson et al. (2011)326 Population did not meet criteria

178

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TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion (continued)

Authors (year) Reason for exclusion

Kaiser et al. (2010)327 Outcomes did not meet criteria

Karatzias et al. (2016)328 Study design did not meet criteria

Kaslow et al. (2010)329 Population did not meet criteria

Kelly et al. (2016)330 Article is a conference abstract

Kelly and Garland (2016)331 Population did not meet criteria

Khazaie et al. (2016)332 Population did not meet criteria

King et al. (2011)333 Article is a conference abstract

King et al. (2016)334 Population did not meet criteria

King et al. (2016)335 Population did not meet criteria

Kip et al. (2013)336 Population did not meet criteria

Kip et al. (2014)337 Outcomes did not meet criteria

Kluepfel et al. (2013)338 Population did not meet criteria

Koehn (2007)339 Study design did not meet criteria

Kozarić-Kovacić et al. (2005)340 Study design did not meet criteria

Kozaric-Kovacic and Pivac (2007)341 Study design did not meet criteria

Kozel et al. (2016)342 Article is a conference abstract

Krakow et al. (2000)343 Population did not meet criteria

Krakow et al. (2001)344 Population did not meet criteria

Kreidler (2005)345 Population did not meet criteria

Krüger et al. (2014)346 Population did not meet criteria

Krystal et al. (2011)99 Population did not meet criteria

Kuckertz et al. (2014)347 Population did not meet criteria

Labrador et al. (2006)348 Non-English language article

Lampe et al. (2008)349 Non-English language article

Lang et al. (2012)350 Article is a study protocol

Lange et al. (2001)351 Population did not meet criteria

Lange et al. (2003)352 Population did not meet criteria

Lange et al. (2003)353 Population did not meet criteria

Largo-Marsh (1996)354 Article is a dissertation

Liebling et al. (2016)355 Intervention did not meet criteria

Liedl et al. (2011)356 Retracted study

Lim et al. (2014)357 Article is a conference abstract

Littleton et al. (2016)358 Population did not meet criteria

Litz et al. (2007)359 Population did not meet criteria

Litz et al. (2012)360 Population did not meet criteria

Long et al. (2011)361 Study design did not meet criteria

Macdonald et al. (2011)362 Population did not meet criteria continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 179 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 3

TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion (continued)

Authors (year) Reason for exclusion

Macklin et al. (2000)363 Study design did not meet criteria

Manteghi et al. (2014)364 Study design did not meet criteria

Margolies et al. (2013)159 Duplicate article

Martenyi et al. (2002)365 Population did not meet criteria

Martenyi et al. (2006)366 Study design did not meet criteria

Matud et al. (2016)367 Non-English language article

Mauritz et al. (2016)368 Article is a study protocol

McFall et al. (2005)369 Intervention did not meet criteria

McGlinchey et al. (2014)370 Intervention did not meet criteria

McWhirter (2011)371 Population did not meet criteria

Mehling et al. (2016)372 Article is a conference abstract

Mehta et al. (2012)373 Article is a conference abstract

Mello et al. (2009)374 Article is a study protocol

Mithoefer et al. (2011)375 Population did not meet criteria

Monson et al. (2006)376 Population did not meet criteria

Monson et al. (2012)377 Intervention did not meet criteria

Morland et al. (2010)378 Comparator did not meet criteria

Morland et al. (2011)379 Comparator did not meet criteria

Morland et al. (2014)380 Comparator did not meet criteria

Morland et al. (2015)381 Comparator did not meet criteria

Moser et al. (2010)382 Comparator did not meet criteria

Mughal et al. (2015)383 Intervention did not meet criteria

Murray et al. (2016)384 Outcomes did not meet criteria

Muzik et al. (2015)385 Intervention did not meet criteria

Nacasch et al. (2011)386 Population did not meet criteria

Nagy et al. (1993)387 Study design did not meet criteria

Nakamura et al. (2011)388 Intervention did not meet criteria

Neuner et al. (2010)389 Population did not meet criteria

Neylan et al. (2001)390 Study design did not meet criteria

Neylan et al. (2003)391 Study design did not meet criteria

Nijdam et al. (2012)392 Population did not meet criteria

Niles et al. (2012)160 Article is a conference abstract

Niles et al. (2013)393 Outcomes did not meet criteria

Nishith et al. (1999)394 Population did not meet criteria

Nishith et al. (2015)395 Study design did not meet criteria

Ochsner Margolies et al. (2012)396 Article is a conference abstract

Oman and Bormann (2015)397 Intervention did not meet criteria

Padala (2006)398 Study design did not meet criteria

180

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion (continued)

Authors (year) Reason for exclusion

Padala et al. (2006)399 Population did not meet criteria

Paivio et al. (2010)400 Comparator did not meet criteria

Paunovic (2011)401 Population did not meet criteria

Peskind et al. (2003)402 Study design did not meet criteria

Petty et al. (2001)403 Study design did not meet criteria

Pigeon et al. (2009)404 Study design did not meet criteria

Pigeon et al. (2015)405 Article is a conference abstract

Pivac and Kozarić-Kovacić (2006)406 Study design did not meet criteria

Pokhariyal et al. (2012)407 Population did not meet criteria

Pollack et al. (2011)408 Population did not meet criteria

Possemato et al. (2011)409 Intervention did not meet criteria

Possemato et al. (2016)410 Comparator did not meet criteria

Price (2005)411 Intervention did not meet criteria

Price (2006)412 Intervention did not meet criteria

Pruiksma et al. (2012)413 Article is a conference abstract

Pruiksma et al. (2013)414 Article is a conference abstract

Ragsdale et al. (1996)415 Population did not meet criteria

Rahman et al. (2016)416 Population did not meet criteria

Randall et al. (1995)417 Study design did not meet criteria

Raskind et al. (2003)418 Study design did not meet criteria

Raskind et al. (2012)419 Article is a conference abstract

Raskind et al. (2013)123 Duplicate article

Raskind (2014)420 Article is a conference abstract

Rauch et al. (2014)421 Article is a conference abstract

Rauch et al. (2015)422 Population did not meet criteria

Ready et al. (2006)423 Study design did not meet criteria

Reed (2004)424 Article is a dissertation

Renner et al. (2011)425 Intervention did not meet criteria

Resick and Schnicke (1992)426 Population did not meet criteria

Resick et al. (2002)427 Population did not meet criteria

Resick et al. (2003)428 Study design did not meet criteria

Resick et al. (2008)429 Comparator did not meet criteria

Resick et al. (2017)430 Comparator did not meet criteria

Rimane and Rosner (2013)431 Article is a study protocol

Robert et al. (2009)432 Study design did not meet criteria

Rodgman et al. (2016)433 Study design did not meet criteria

Rosenbaum et al. (2015)434 Intervention did not meet criteria continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 181 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 3

TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion (continued)

Authors (year) Reason for exclusion

Rothbaum (1997)435 Population did not meet criteria

Rothbaum et al. (2001)436 Study design did not meet criteria

Rothbaum et al. (2005)437 Population did not meet criteria

Rothbaum et al. (2008)438 Study design did not meet criteria

Rothbaum et al. (2014)129 Study design did not meet criteria

Ryan et al. (2005)439 Intervention did not meet criteria

Sachsse et al. (2006)440 Study design did not meet criteria

Sack et al. (2017)441 Outcomes did not meet criteria

Salloum et al. (2015)442 Intervention did not meet criteria

Sautter et al. (2015)443 Intervention did not meet criteria

Schaal et al. (2009)444 Comparator did not meet criteria

Schnurr et al. (2003)445 Population did not meet criteria

Schnurr et al. (2007)446 Population did not meet criteria

Schnurr et al. (2009)447 Outcomes did not meet criteria

Schnurr and Lunney (2015)448 Study design did not meet criteria

Schnurr and Lunney (2016)449 Study design did not meet criteria

Seppälä et al. (2014)450 Intervention did not meet criteria

Sezgin and Punamäki (2008)451 Study design did not meet criteria

Shearing et al. (2011)452 Population did not meet criteria

Short (2005)453 Study design did not meet criteria

Silver et al. (1995)454 Study design did not meet criteria

Skinhoj et al. (2001)455 Study design did not meet criteria

Smith et al. (2012)456 Study design did not meet criteria

Spence et al. (2014)457 Population did not meet criteria

Spiegel et al. (2004)458 Study design did not meet criteria

Stade et al. (2015)459 Intervention did not meet criteria

Stalker and Fry (1999)460 Study design did not meet criteria

Steil et al. (2011)461 Article is a conference abstract

Stein et al. (2006)462 Study design did not meet criteria

Steinert et al. (2017)463 Population did not meet criteria

Steuwe et al. (2016)464 Study design did not meet criteria

Stovall-McClough and Cloitre (2003)465 Study design did not meet criteria

Su et al. (2007)466 Non-English language article

Sulejmanpasic-Arslanagic and Bise Srebrenka (2015)467 Article is a conference abstract

Surís et al. (2010)468 Intervention did not meet criteria

Surís et al. (2013)469 Population did not meet criteria

Swanson et al. (2009)470 Study design did not meet criteria

Taing et al. (2011)471 Article is a conference abstract

182

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

TABLE 27 Studies excluded at full-text screening stage, with reasons for exclusion (continued)

Authors (year) Reason for exclusion

Talbot et al. (2011)472 Population did not meet criteria

Talbot et al. (2014)473 Population did not meet criteria

Tan et al. (2011)474 Comparator did not meet criteria

Tarquinio et al. (2012)475 Population did not meet criteria

Tarrier and Sommerfield (2004)476 Population did not meet criteria

Thomaes et al. (2015)477 Non-English language article

Thorp et al. (2012)478 Study design did not meet criteria

Tourigny et al. (2005)479 Non-English language article

Truijens and Van Emmerik (2014)480 Population did not meet criteria

van den Berg and van der Gaag (2012)481 Population did not meet criteria

van der Kolk et al. (2007)482 Population did not meet criteria

van Emmerik et al. (2008)483 Population did not meet criteria

Vera et al. (2011)484 Population did not meet criteria

Villarreal et al. (2007)485 Study design did not meet criteria

Villarreal et al. (2010)486 Study design did not meet criteria

Vitriol et al. (2009)487 Intervention did not meet criteria

Weine et al. (2008)488 Intervention did not meet criteria

Wells and Colbear (2012)489 Population did not meet criteria

Westbury and Tutty (1999)490 Intervention did not meet criteria

Wood et al. (2011)491 Study design did not meet criteria

Yeh et al. (2011)492 Population did not meet criteria

Yehua (2003)493 Study design did not meet criteria

Yehuda et al. (2015)494 Population did not meet criteria

Yuen et al. (2015)495 Comparator did not meet criteria

Ziemba (et al. 2014)496 Comparator did not meet criteria

Zimmermann et al. (2005)497 Non-English language article

Zimmermann et al. (2007)498 Study design did not meet criteria

Zisook et al. (2000)499 Study design did not meet criteria

Zlotnick et al. (2011)500 Population did not meet criteria

Zoellner et al. (1999)501 Population did not meet criteria

Zohar et al. (2002)147 Duplicate article

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 183 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 4 Characteristics of randomised controlled trials included

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 185 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. 186 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions

www.journalslibrary.nihr.ac.uk Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional) Acarturk et al. EMDR EMDR; SCTF Waitlist Duration: NR Face to face; community/refugee camp; (2015)53 Turkish psychologists trained at level 1 Frequency: NR EMDR, supervised by EMDR institute accredited trainer Length of sessions: seven sessions, 90 minutes each

Acarturk et al. EMDR EMDR; SCTF Waitlist Duration: 5 weeks Face to face/online; community/ (2016)54 refugee camp; psychologists trained in Frequency: NR EMDR

Length of sessions: NR

Adenauer et al. NET TFCBT; SCTF Waitlist Duration: NR Face to face; setting NR; clinical (2011)55 psychologists Frequency: weekly or biweekly

Length of sessions: 12 sessions, average length 108 minutes (SD 17 minutes)

Azad Marzabadi MBSR Mindfulness; SCNTF Waitlist/continued Duration: 4 weeks Face to face; hospital; psychologist and Hashemi Zadeh treatment (2014)57 Frequency: twice a week

Length of sessions: eight sessions, 90 minutes each

Bichescu et al. NET TFCBT; MCTF Psychoeducation Duration: 5 weeks Face to face, individual; setting NR; (2007)61 trained PhD psychology student Frequency: weekly or biweekly

Length of sessions: 120 minutes erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Beidel et al. (2011)60 Trauma management TFCBT; MCTF Duration: 17 weeks Face to face, individual and group; therapy with exposure setting NR; doctoral-level therapists Frequency: exposure three times per week; social and emotional rehabilitation twice a week (2 weeks), weekly for 10 weeks

Length of sessions: 14 sessions of exposure, length NR. Social and emotional rehabilitation 90 minutes

Exposure-only therapy Exposure only Duration: 17 weeks

Frequency: three times per week

Length of sessions:14 sessions of tal. et

exposure, 14 sessions of psychoeducation 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Bolton et al. Behavioural activation NTFCBT; SCNTF Waitlist Duration: NR Face to face, individual; primary health (2014)62 treatment for depression clinics and one outpatient clinic; Frequency: NR community mental health workers (nurses, pharmacist assistants or Length of sessions: 12 sessions, length NR physician assistants) with a mental health background CPT TFCBT; SCTF Duration: NR

Frequency: NR

Length of sessions: 12 sessions, length NR

Buhmann et al. CBT TFCBT; NA Waitlist Duration: 6 months Face to face; mental health clinic; (2016)63 doctors and therapists with mental Frequency: weekly health background o.2 o 43 No. 24 Vol. Length of sessions: 16 sessions, length NR continued 187 188 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions (continued)

Carlson et al. EMDR biofeedback EMDR; SCTF Waitlist Duration: 6 weeks Face to face, individual; clinic based; (1997)64 relaxation experienced therapists, EMDR trained Frequency: twice a week therapists with research and clinical backgrounds Length of sessions: 12 sessions, 60–75 minutes each

Biofeedback relaxation NTFCBT; SCNTF Duration: 6 weeks Face to face, individual; clinic based; experienced therapists with Frequency: twice a week behavioural, psychodynamic and biofeedback backgrounds Length of sessions: 12 sessions, 40 minutes each

Chard (2005)66 CPT for sexual abuse TFCBT; MCTF Waitlist Duration: 17 weeks Face to face, individual and group; survivors Centre for Traumatic Stress Studies; Frequency: weekly individual and group graduate psychology students with sessions background in behavioural interventions and mental health Length of sessions: group sessions 90 minutes, individual sessions 60 minutes

Classen et al. Trauma-focused therapy NA; NA (data were Waitlist Duration: 24 weeks Face to face, group; setting NR; (2001)68 presented together) experienced group leaders supervised Frequency: weekly by an expert in trauma (therapists included psychologists and one Length of sessions: 90 minutes licensed MFCC)

Present-centred therapy Duration: 24 weeks

Frequency: weekly

Length of sessions: 90 minutes erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Cloitre et al. (2002)69 STAIR-modified PE DBT; MCTF Minimal attention Duration: 12 weeks Face to face, individual; setting NR; waitlist and clinical psychologist support/exposure Frequency: weekly STAIR/twice weekly modified PE

Length of sessions: 16 sessions, STAIR 60 minutes, modified PE 90 minutes

STAIR/exposure DBT; MCTF Duration: 16 weeks Face to face, individual; setting NR; master’s/doctorate psychologist/social Frequency: weekly work staff/expert clinicians with mental health backgrounds Length of sessions: NR tal. et STAIR/support DBT; MCNTF Duration: 16 weeks Face to face, individual; setting NR; 2020 Assessment Technology Health master’s/doctorate psychologist/social ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Frequency: weekly work staff/expert clinicians with mental health backgrounds Length of sessions: NR

Cook et al. (2010)71 Imagery rehearsal TFCBT; MCTF Duration: 6 weeks Face to face, group; setting NR; therapy psychologists and psychiatric nurse Frequency: weekly

Length of sessions: 90 minutes

Sleep and nightmare Duration: 6 weeks management Frequency: weekly Length of sessions: 90 minutes

continued 43 No. 24 Vol. 189 190 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions (continued)

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

www.journalslibrary.nihr.ac.uk Devilly et al. EMDR EMDR; SCTF Standard psychiatric Duration: NR Face to face, individual; setting NR; (1998)74 support active clinician trained by Shapiro502 Frequency: NR

Length of sessions: two sessions, 90 minutes

Reactive eye dilatation EMDR; SCTF Duration: NR desensitisation and reprocessing Frequency: NR

Length of sessions: two sessions, 90 minutes

Edmond et al. EMDR EMDR; SCTF Delayed treatment Duration: 6 weeks Face to face; setting NR; white female (1999)76 master’s-level therapists Frequency: weekly

Length of sessions: 90 minutes

Routine individual Duration: 6 weeks treatment Frequency: weekly Length of sessions: 90 minutes

Engel et al. (2015)78 Delivery of self training NTFCBT; SCNTF Optimised usual Duration: 6 weeks Computer/telephone; remote setting; and education for care online/nurse support stressful situations Frequency: three times per week (DESTRESS-PC) Length of sessions: 18 sessions, log in 15–30 minutes, homework 30 minutes

Feske (2008)79 PE TFCBT; SCTF Treatment as usual Duration: 12 weeks Face to face, individual (individual and group for controls); community clinic Frequency: weekly setting; trained master’s-level social workers and a nurse with a mental Length of sessions: 9–12 total sessions, health background PE 90 minutes, treatment as usual 60 minutes erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Franklin et al. PE by iPhone (Apple Inc., TFCBT; SCTF Treatment as usual Duration: 10 weeks iPhone-based video chat; (2017)81 Cupertino, CA, USA) teleconference at community VA Frequency: 10 sessions within 12 weeks centre; psychologists

Length of sessions: NR

PE by computer-based TFCBT; SCTF Treatment as usual Duration: 10 weeks Computer-based teleconference; teleconferencing teleconference at community VA Frequency: 10 sessions within 12 weeks centre; psychologists

Length of sessions: NR

Gamito et al. Virtual reality exposure TFCBT; SCTF Waitlist Duration: NR Face to face, individual; setting NR; (2010)83 therapy professional NR Frequency: NR

Length of sessions: 12 sessions, length NR tal. et elhTcnlg seset2020 Assessment Technology Health Exposure in imagination TFCBT; SCTF Duration: NR Computer-based teleconference; ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under teleconference at community VA Frequency: NR centre; psychologists

Length of sessions: 12 sessions, length NR

Germain et al. Behavioural sleep TFCBT; MCTF Placebo Duration: 8 weeks Face to face; setting NR; master’s-level (2012)84 intervention therapist with mental health Frequency: weekly background

Length of sessions: eight sessions, 45 minutes each

Hermenau et al. NET for forensic TFCBT; SCTF No intervention Duration: 2 weeks Face to face (individual and group); (2013)86 offender rehabilitation non-governmental organisation (FORNET) Frequency: approximately every other day reintegration centre for war-affected young people; therapists with a mental 43 No. 24 Vol. Length of sessions: 1–2 hours health background continued 191 192 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions (continued)

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional) www.journalslibrary.nihr.ac.uk Hijazi et al. (2014)87 Brief NET TFCBT; SCTF Waitlist Duration: 3 weeks Face to face; private room setting according to participant preference Frequency: weekly (e.g. own home, church, community centre); therapists trained by a licensed Length of sessions: 60–90 minutes psychologist with expertise in exposure therapies

Himmerich et al. Inpatient psychotherapy EMDR; MCNTF Outpatient clinical Duration: 6 weeks Face to face; hospital; professionals (2016)88 management NR, but with mental health background Frequency: NR

Length of sessions: inpatient

Hinton et al. CBT TFCBT; SCTF Delayed treatment Duration: 11 weeks Face to face, individual; setting NR; (2004)90 trained CBT therapist with cultural Frequency: weekly facilitators

Length of sessions: NR

Hinton et al. CBT TFCBT; SCTF Delayed treatment Duration: 12 weeks Face to face, individual; setting NR; (2005)89 psychiatrist Frequency: weekly

Length of sessions: NR

Jensen (1994)91 EMDR EMDR; SCTF Treatment as usual Duration: NR Face to face; setting NR; trained with option of therapist with mental health delayed EMDR Frequency: NR background

Length of sessions: NR

Jung and Steil Cognitive restructuring TFCBT; MCTF Waitlist Duration: NR Face to face/use of internet; specialist (2013)92 and imagery modification PTSD outpatient centres; one at Frequency: NR university and two at large psychiatric hospitals; therapist supervised by Length of sessions: two sessions, senior therapist (both authors) treatment 90 minutes, booster 50 minutes erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI:

rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Katz et al. (2014)93 Holographic Other psychotherapy; Person-centred Duration: 10 weeks Face to face, individual; setting NR; reprocessing MCNTF control psychologist, clinical social workers, Frequency: weekly psychology post-docs, marriage and family therapist trainees and psychiatry Length of sessions: NR residents, with mental health backgrounds

PE TFCBT; SCTF Waitlist Face to face/use of internet; specialist PTSD outpatient centres; one at university and two at large psychiatric hospitals; therapist supervised by senior therapist (both authors)

Keane et al. (1989)94 Implosive (flooding) TFCBT; SCTF Waitlist Duration: NR Face to face (individual); VA medical therapy centre; therapist with mental health Frequency: NR background

Length of sessions: 14 sessions (plus an additional two sessions if deemed tal. et appropriate by therapist), 90 minutes 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Kearney et al. MBSR and treatment as Mindfulness; SCNTF Treatment as usual Duration: 8 weeks Face to face (group); VA medical (2013)95 usual centre; professional instructors with Frequency: weekly mental health backgrounds

Length of sessions: 2.5 hours (plus 7-hour retreat)

King et al. (2013)148 Mindfulness-based Treatment as Duration: 8 weeks Face to face (group); PTSD outpatient cognitive therapy group usual (PTSD clinic (for veterans); therapists with a psychoeducation Frequency: weekly mental health background, including and skills group or clinical psychologists imagery rehearsal Length of sessions: 8 hours therapy group)

Knaevelsrud et al. Internet-based CBT TFCBT; SCTF Waitlist Duration: 5 weeks Computer; remote (web-based) setting; (2015)96 psychotherapists or psychiatrists 43 No. 24 Vol. Frequency: twice a week

Length of sessions: not fixed continued 193 194 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions (continued)

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Krupnick et al. IPT IPT; SCNTF Waitlist Duration: 16 weeks Face to face, group; setting NR; clinical www.journalslibrary.nihr.ac.uk (2008)98 psychologists Frequency: weekly

Length of sessions: 2 hours

Kubany et al. Cognitive trauma TFCBT; MCTF Waitlist Duration: 4 weeks Face to face (individual); setting NR; (2004)100 therapy for battered therapist women Frequency: NR

Length of sessions: 1.5 hours, 8.5 mean total sessions

Kubany et al. Cognitive trauma TFCBT; MCTF Delayed treatment Duration: 4–6 weeks Face to face, individual; setting NR; (2004)101 therapy for battered professionals included clinical women Frequency: twice a week psychologist, advanced degree nurses, master’s in counselling psychology, Length of sessions: 60 minutes, 8–11 total victim witness advocate, baccalaureate sessions degree and several years of experience in domestic violence counselling

Lande et al. Biofeedback and Biofeedback; NA Treatment as usual Duration: 3 weeks Face to face (individual) via computer; (2010)102 treatment as usual specialist psychiatric outpatient clinic; Frequency: twice a week computer, professional NR

Length of sessions: 20 minutes

Lau and Kristensen Analytic group Other psychotherapy; Treatment as usual Duration: 52 weeks Face to face (group); outpatient mental (2007)103 psychotherapy MCNTF health services; therapists with a Frequency: weekly mental health background Systemic group Other psychotherapy; psychotherapy MCNTF Length of sessions: 2.25 hours

Margolies et al. CBT for insomnia with TFCBT; MCTF Minimal attention Duration: 8 weeks Face to face, individual; VA medical (2011)105 imagery rehearsal waitlist and waitlist centre; clinical psychologist therapy Frequency: NR

Length of sessions: 60 minutes; four individual sessions, with break between second and third sessions erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

McDonagh et al. CBT TFCBT; SCTF Minimal attention Duration: 14 weeks Face to face, individual; setting NR; (2005)106 waitlist psychologists and master’s-level clinical Frequency: weekly social workers

Length of sessions: 2 hours for first seven sessions, 1.5 hours for final seven sessions

Present-centred therapy Other psychotherapy; Duration: 14 weeks MCNTF Frequency: weekly

Length of sessions: 2 hours for first seven sessions, 1.5 hours for final seven sessions

McLay et al. Virtual reality graded TFCBT; SCTF Waitlist Duration: 10 weeks Face to face, individual; navy medical (2011)107 exposure therapy facilities; psychologist Frequency: up to twice a week, closer to weekly tal. et elhTcnlg seset2020 Assessment Technology Health Length of sessions: NR ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Meffert et al. IPT IPT; SCNTF Waitlist Duration: 3 weeks Face to face; private rooms of (2014)108 community-based support organisation; Frequency: twice a week members of Sudanese community without mental health background Length of sessions: NR

Miyahira et al. Add-on virtual reality TFCBT; SCTF Minimal attention Duration: 5 weeks Face to face; setting NR; therapist with (2012)109 exposure training on manualised CBT treatment Frequency: twice a week protocol with virtual reality exposure

Length of sessions: NR

Moradi et al. Memory specificity NTFCBT; SCNTF Treatment as usual Duration: 4 consecutive weeks Face to face/group/individual; specialist (2014)111 training military hospital; clinical psychologist Frequency: weekly 43 No. 24 Vol.

Length of sessions: four sessions, one hour continued 195 196 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions (continued)

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional) www.journalslibrary.nihr.ac.uk Neuner et al. NET TFCBT; SCTF Monitoring Duration: 3 weeks Face to face; setting NR; lay (2008)113 counsellors without mental health Frequency: twice a week background

Length of sessions: 2 hours

Trauma counselling TFCBT; SCTF Duration: 3 weeks

Frequency: twice a week

Length of sessions: 2 hours

Neuner et al. NET TFCBT; SCTF Psychoeducation Duration: 3 weeks Face to face (individual); setting NR; (2004)114 doctoral-level psychologists or Frequency: four sessions in 3 weeks graduate students with experience in other therapies (e.g. counselling) Length of sessions: 90 minutes (up to 120 minutes in exceptional circumstances) Supportive counselling TFCBT; SCTF Duration: 3 weeks

Frequency: four sessions in 3 weeks

Length of sessions: 90 minutes (up to 120 minutes in exceptional circumstances)

Niles et al. (2012)115 Mindfulness Mindfulness; SCNTF Psychoeducation Duration: 8 weeks Remotely (individual); mostly home-based; two female clinicians Frequency: weekly with PhDs in clinical psychology served as therapists Length of sessions: 45 minutes in-person sessions, 20 minutes telephone sessions

Owens et al. CPT for sexual abuse TFCBT; SCTF Minimal attention Duration: 17 weeks Face to face, individual and group; (2001)117 setting NR; professionals NR Frequency: NR

Length of sessions: NR erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Paunovic and Ost CBT TFCBT; SCTF Minimal attention Duration: 4–5 months Face to face, individual; setting NR; (2001)119 clinical psychology doctoral student Frequency: weekly

Length of sessions: NR

Exposure-only therapy Exposure only; SCTF Duration: 4–5 months

Frequency: weekly

Length of sessions: 20 minutes

Polusny et al. MBSR Mindfulness; SCNTF Duration: 9 weeks Face to face, group; VA medical centre; (2015)120 instructors and doctoral-level clinicians tal. et Frequency: weekly 2020 Assessment Technology Health ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Length of sessions: 2.5 hours

Present-centred therapy Other psychotherapy; Duration: 9 weeks SCNTF Frequency: weekly

Length of sessions: 1.5 hours

Possemato et al. Primary care brief Mindfulness; SCNTF Primary care Duration: 4 weeks Face to face individual/group; VA (2016)121 mindfulness training treatment as usual medical centre; physicians expert in Frequency: weekly MBSR practitioners and certified instructors Length of sessions: 1.5 hours

continued 43 No. 24 Vol. 197 198 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions (continued)

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of www.journalslibrary.nihr.ac.uk Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Ready et al. Virtual reality exposure TFCBT; SCTF Duration: NR Face to face, individual; setting NR; (2010)124 professional NR Frequency: NR

Length of sessions: 90 minutes, 10 sessions Present-centred therapy Other psychotherapy; Duration: NR SCNTF Frequency: NR

Length of sessions: 90 minutes, 10 sessions

Reed and Enright Forgiveness therapy Other psychotherapy; Alternative therapy Duration: 5–12 months Face to face, individual; setting NR; (2006)125 SCNTF trained psychiatric nurse Frequency: weekly

Length of sessions: 1 hour, average duration 7.95 months

Reger et al. (2016)126 Virtual reality exposure TFCBT; SCTF Waitlist Duration: 5 weeks Face to face (individual); army military installation; doctoral-level clinicians Frequency: weekly or twice weekly

Length of sessions: 1.5–2 hours, 10 sessions in total

PE TCBT; SCTF Duration: 5 weeks

Frequency: weekly or twice weekly

Length of sessions: 1.5–2 hours, 10 sessions in total erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Resick et al. CPT – cognitive-only TFCBT; SCTF Duration: NR Face to face, group; setting NR; civilian (2015)128 version therapists with mental health Frequency: twice a week background

Length of sessions: 90 minutes, 12 sessions in total

Present-centred therapy Other psychotherapy; Duration: NR SCNTF Frequency: twice a week

Length of sessions: 90 minutes, 12 sessions in total

Rogers et al. EMDR EMDR; SCTF Duration: one session Face to face, individual; setting NR; (1999)130 trained therapist with mental health Frequency: once background tal. et Length of sessions: 60–90 minutes 2020 Assessment Technology Health ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Exposure (implosive Exposure only; SCTF Duration: one session flooding) Frequency: once

Length of sessions: 60–90 minutes

Sikkema et al. HIV and trauma coping NTFCBT; SCNTF Waitlist Duration: 15 weeks Face to face; community clinics; clinical (2007)131 group psychologists/clinical social workers Frequency: weekly

Length of sessions: 90 minutes

Support group NTFCBT; SCNTF Duration: 15 weeks

Frequency: weekly 43 No. 24 Vol.

Length of sessions: 90 minutes continued 199 200 PEDX4 APPENDIX IRJunl Library Journals NIHR TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions (continued)

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Sikkema et al. Coping skills programme NTFCBT; SCNTF HIV support group Duration: 15 weeks Face to face (group); community health (2013)132 centre; therapists with a mental health www.journalslibrary.nihr.ac.uk Frequency: weekly background

Length of sessions: 90 minutes Stenmark et al. NET TFCBT; SCTF Treatment as usual Duration: 10 weeks Face to face, individual; setting NR; (2013)136 professionals included psychologists, Frequency: weekly psychiatrists, psychiatric nurses, occupational therapists, drama Length of sessions: 90 minutes therapists, clinical social workers

Teng et al. (2008)137 Panic control treatment NTFCBT; SCNTF Psychoeducational Duration: 10 weeks Face to face (individual); VA hospital; supportive master’s-level clinicians treatment (PE-SUP) Frequency: weekly

Length of sessions: 1 hour

Ter Heide et al. EMDR EMDR; SCTF Duration: 11 weeks Face to face, individual; centre for (2011)138 psychotrauma; psychotherapists, Frequency: weekly psychiatrist, health-care psychologists

Length of sessions: 90 minutes (60 minutes dedicated to EMDR)

Stabilisation EMDR; SCNTF Duration: 11 weeks Face to face, individual; centre for psychotrauma; clinical psychologist, Frequency: weekly physician/psychotherapist, physician, social-psychiatric nurses Length of sessions: 60 minutes

Ter Heide et al. EMDR EMDR; SCTF Duration: 9 weeks Face to face (individual); treatment (2016)139 centre for CPTSD; clinical Frequency: NR psychologists and psychotherapists

Length of sessions: 12 hours overall

Stabilisation as usual Stabilisation; SCNTF Duration: 9 weeks

Frequency: NR

Length of sessions: 12 hours overall erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional)

Ulmer et al. Sleep intervention for TFCBT; MCTF Usual care Duration: 12 weeks Face to face, individual; setting NR; (2011)140 PTSD clinical psychologist Frequency: fortnightly

Length of sessions: 1 hour

Wahbeh et al. Mindfulness meditation Mindfulness; SCNTF Sitting quietly Duration: 6 weeks Face to face and remote, individual; (2016)142 setting NR; research assistant Frequency: weekly

Length of sessions: 20 minutes

Slow breathing with Biofeedback; SCNTF Duration: 6 weeks biofeedback device (mindfulness meditation Frequency: weekly and slow breathing) tal. et Length of sessions: 20 minutes 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Slow breathing Other psychological Duration: 6 weeks intervention; SCNTF Frequency: weekly

Length of sessions: 20 minutes

Wang et al. Biofeedback-supported TFCBT; MCTF Waitlist Duration: 10 weeks Face to face (individual and group); (2016)143 CBT and group therapy rehabilitation centre (for torture (physiotherapy and Frequency: twice a week victims); therapists and exercises) physiotherapists with mental health Length of sessions: group sessions 60–90 backgrounds minutes, individual sessions 90 minutes (60 minutes for CBT intervention, 15- to 20-minute period of breathing training using a biofeedback device, 10–15 o.2 o 43 No. 24 Vol. minutes for reviewing and note taking) continued 201 202 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 28 Intervention characteristics for the randomised controlled studies included comparing psychological interventions (continued)

Intervention category; Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) superordinate category Control(s) length of sessions) professional) www.journalslibrary.nihr.ac.uk Weiss et al. (2015), CETA TFCBT; MCTF Waitlist Duration: 8–12 weeks Face to face, individual; community; trial 1: CETA144 community mental health workers Frequency: weekly

Length of sessions: 50–60 minutes, 8–12 sessions in total

Weiss et al. (2015), CPT TFCBT; SCTF Waitlist Duration: 12 weeks Face to face, individual; community; trial 2: CPT144 community mental health workers Frequency: weekly

Length of sessions: NR

Yeomans et al. Workshop with Other psychotherapy; Waitlist Duration: 4 days Face to face, group; community; local (2010)145 psychoeducation MCTF facilitators without a mental health Frequency: 3 consecutive days and background 1-month follow-up

Length of sessions: day long

Workshop without Other psychotherapy; Duration: 4 days psychoeducation SCTF Frequency: 3 consecutive days and 1-month follow-up

Length of sessions: day long

Zlotnick et al. Affect management Waitlist Duration: 15 weeks Face to face (group); setting NR; (1997)146 therapist with mental health Frequency: weekly background

Length of sessions: 2 hours CETA, common elements treatment approach; CPT, cognitive processing therapy; MCTF, multicomponent trauma-focused; MCNTF, multicomponent non-trauma-focused; MFCC, Marriage, Family and Child Counsellor; NTFCBT, non-trauma-focused CBT; PE, prolonged exposure; SCNTF, single-component non-trauma-focused; SCTF, single-component trauma-focused; TFCBT, trauma-focused CBT; VA, veterans’ affairs. DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

TABLE 29 Intervention characteristics for randomised controlled studies included comparing pharmacological interventions

Intervention Author (year) Intervention(s) category Control(s) Intensity (duration, frequency and dose)

Rezaei Ardani Rivastigmine Rivastigmine Placebo (in Rivastigmine augmented therapy of et al. (2017)56 augmented combination with citalopram and sodium valproate therapy citalopram and sodium valproate) Duration: 12 weeks

No intervention Frequency: twice a day

Dose: Weeks 1–4 1.5 mg twice a day, Week 5 3 mg twice a day in addition to citalopram 40 mg/day and sodium valproate 20 mg/kg/day

Bartzokis et al. Risperidone Antipsychotic Placebo First 4 weeks delivered in conjunction (2005)58 with an inpatient psychosocial programme. The remainder of the intervention was delivered as an outpatient programme.

Duration: 16 weeks

Frequency: NR

Dose: initiated at 1 mg, increased to 3 mg bedtime dose (over 2 weeks); maintained at 3 mg

Becker et al. Bupropion SR Antidepressant Placebo Duration: 8 weeks (2007)59 Frequency: once or twice a day

Dose: 100 mg/day for 2 weeks. Dose increased to 100 mg twice a day as indicated. No significant improvement at 4 weeks resulted in a maximum dose of 150 mg twice a day

Celik et al. Paroxetine SSRI/antidepressant Duration: 8 weeks (2011)65 Frequency: once a day

Dose: initiated at 10 mg/day for Week 1, then increased to 20 mg for Weeks 2 and 3, 30 mg for Weeks 4 and 5, 40 mg for Weeks 6 and 7 and 60 mg for Weeks 8–12 (if tolerated/clinically indicated) Amitriptyline Antidepressant Duration: 8 weeks

Frequency: once a day

Dose: initiated at 75 mg/day for Weeks 1–3 (initial dose of 25 mg for Days 1–3, 50 mg for Days 4–7 and 75 mg for Days 8–21), then increased to 100 mg from Week 4 (as necessary) and up to 200 mg or down to 75 mg from Week 5 (as necessary) continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 203 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 4

TABLE 29 Intervention characteristics for randomised controlled studies included comparing pharmacological interventions (continued)

Intervention Author (year) Intervention(s) category Control(s) Intensity (duration, frequency and dose)

Chung et al. Mirtazapine Antidepressant Duration: 6 weeks (2004)67 Frequency: daily

Dose: initiated at mean dose of 19.1 ± 8.53 mg/day, Weeks 1–2 31.5 ± 9.13 mg/day, Weeks 2–6 38.5 ± 12.10 mg/day

Sertraline SSRI/antidepressant Duration: 6 weeks

Frequency: daily

Dose: initiated at 58.2 ± 24.15 mg/day, Weeks 1–2 89.8 ± 23.89 mg/day and Weeks 2–6 115.3 ± 36.02 mg/day

Mean daily dose: mirtazapine 34.1 mg, sertraline 101.5 mg

Davis et al. Nefazodone Antidepressant Placebo Duration: 12 weeks (2004)73 Frequency: twice a day

Dose: initiated at 100 mg, increased by 100 mg every 4 days as tolerated, up to a maximum benefit (not exceeding 600mg/day)

Davis et al. Divalproex Anticonvulsant Placebo Duration: 8 weeks (2008)72 Frequency: twice a day

Dose: initiated at 500 mg twice a day, increased by 500 mg as tolerated to a maximum of 3000 mg/day

Friedman et al. Sertraline SSRI/antidepressant Placebo Duration: 12 weeks (2007)82 Frequency: daily

Dose: initiated at 25 mg/day, Week 2 increased dose to 50 mg/day where dose-limiting adverse events did not present. Subjects who failed to respond received titrated weekly increment of 50 mg up to a maximum of 200 mg/day

Germain et al. Prazosin Prazosin Placebo Duration: 8 weeks (2012)84 Frequency: daily

Dose/length of sessions: initiated at 1 mg, increasing over the following weeks to 2 mg, 4 mg, 6 mg, 10 mg and 15 mg. Final mean dose 8.9 mg

204

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TABLE 29 Intervention characteristics for randomised controlled studies included comparing pharmacological interventions (continued)

Intervention Author (year) Intervention(s) category Control(s) Intensity (duration, frequency and dose)

Hamner et al. Adjunctive Antipsychotic Placebo Risperidone added to regimen of (2003)85 risperidone antidepressant treatment (fluoxetine, nefazadone, paroxetine, sertraline, buprioprion)

Duration: 5 weeks

Frequency: daily

Dose: initiated at 1 mg/day, increased to a maximum of 6 mg/day

Krystal et al. Adjunctive Antipsychotic Placebo Adjunctive risperidone with ongoing (2011)99 risperidone pharmacotherapy

Duration: 24 weeks

Frequency: daily

Dose: initiated at 1 mg at night. Increased by 1 mg/week to 3 mg. After 4 weeks, a further 1 mg increase could be made if tolerated and clinically indicated

Lindley et al. Topiramate Anticonvulsant Placebo Duration: 7 weeks (2007)104 Frequency: daily

Dose: initiated at 25 mg, increased by 50 mg each week until maximum toleration or 200 mg/day

Monnelly et al. Risperidone Antipsychotic Placebo Duration: 6 weeks (2003)110 Frequency: daily

Dose: initiated at 0.5 mg, increased fortnightly to maximum 2 mg/day

Naylor et al. Paroxetine SSRI/antidepressant Placebo Duration: 12 weeks (2013)112 Frequency: daily

Dose: flexible dosing 10–40 mg/day depending on tolerance and response

Otto et al. Sertraline SSRI/antidepressant Compared Duration: NR (2003)116 with SSRI/ antidepressant Frequency: daily with TFCBT; see Table 30 Dose/length of sessions: sertraline initiated at 25 mg, titrated 50 mg each week to maximum 200 mg. Mean final dose 125 mg/day

Panahi et al. Sertraline SSRI/antidepressant Placebo Duration: 10 weeks (2011)118 Frequency: daily

Dose: initiated at 50 mg/day, flexible adjustment fortnightly to a maximum of 200 mg/day continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 205 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 4

TABLE 29 Intervention characteristics for randomised controlled studies included comparing pharmacological interventions (continued)

Intervention Author (year) Intervention(s) category Control(s) Intensity (duration, frequency and dose)

Raskind et al. Prazosin Prazosin Placebo Duration: 8 weeks (2007)122 Frequency: daily

Dose: initiated at 1 mg/nightly for 3 days. Days 3–7 increased to 2 mg/day based on response. Persistence of traumatic nightmares increased dose to 2 mg per week up to 10 mg/day at Day 28. Persistent lack of response allowed additional 5 mg to a maximum of 15 mg/day. Mean daily dose of prazosin was 13 (3) mg and of placebo capsules was 14 (2) mg

Raskind et al. Prazosin Prazosin Placebo Duration: 15 weeks (2013)123 Frequency: once or twice daily

Dose: titrated 1–2 mg/day, depending on gender. Week 2: males (AM 1 mg, PM 4 mg), females (AM 1 mg, PM 2 mg); Week 3: males (AM 2 mg, PM 6 mg), females (AM 1 mg, PM 2 mg); Week 4: males (AM 2 mg, PM 10 mg), females (AM 2 mg, PM 6 mg); Week 5: males (AM 5 mg, PM 15 mg), females (AM 2 mg, PM 10 mg); Week 6: males (AM 5 mg, PM 20 mg), females (AM 2 mg, PM 10 mg) Reich et al. Risperidone Antipsychotic Placebo Duration: 8 weeks (2004)127 Frequency: daily (can be divided into two or three doses)

Dose: initiated at 0.5 mg/day, increased to 1 mg/day at 3 days, then increased by 1 mg/day for 1 week up to target dose of 4 mg/day until symptom relief reported. Dosage increased to maximum of 8 mg/day if lack of response by Week 5

Smajkic et al. Paroxetine SSRI/antidepressant Duration: 6 weeks (2001)133 Frequency: daily

Dose: 20 mg once daily for 14 days then, if tolerated at 2 weeks, the dosage was continued Sertraline SSRI/antidepressant Duration: 6 weeks

Frequency: daily

Dose: 50 mg once daily for 14 days then, if tolerated at 2 weeks, 100 mg once daily

Venlafaxine Antidepressant Duration: 6 weeks

Frequency: twice a day

Dose: 37.5 mg twice daily for 14 days then, if tolerated at 2 weeks, 75 mg twice daily

206

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TABLE 29 Intervention characteristics for randomised controlled studies included comparing pharmacological interventions (continued)

Intervention Author (year) Intervention(s) category Control(s) Intensity (duration, frequency and dose)

Stein et al. Adjunctive Antipsychotic Placebo Adjunctive olanzapine for subjects (2002)135 olanzapine minimally responsive to SSRIs at maximally tolerated doses

Duration: 8 weeks

Frequency: daily

Dose: initiated at 10 mg, increased to 20 mg after 2 weeks if clinically indicated and tolerated

van der Kolk Fluoxetine SSRI/antidepressant Placebo Duration: 5 weeks et al. (1994)141 Frequency: daily

Dose: initiated at 20 mg/day, increased weekly to a maximum of 60 mg

Zohar et al. Sertraline SSRI/antidepressant Placebo Duration: 10 weeks (2002)147 Frequency: daily

Dose: initiated at 50 mg/day, flexible titration in 50 mg increments fortnightly up to a maximum of 200 mg

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 207 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. 208 PEDX4 APPENDIX IRJunl Library Journals NIHR

TABLE 30 Intervention characteristics for randomised controlled studies included comparing combined psychological and pharmacological interventions

Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) Intervention categories Control(s) strength of dose/length of sessions) professional) www.journalslibrary.nihr.ac.uk Buhmann et al. Sertraline, SSRI/antidepressant and Waitlist Duration: 6 months Face to face; mental health clinic; (2016)63 psychoeducation and TFCBT doctors and therapists with mental CBT Frequency: psychoeducation and CBT health background weekly, sertraline daily

Dose/length of sessions: 10 consultations and 16 sessions of CBT

Sertraline increased by 25–50 mg to a maximum dose of 200 mg. Mianserin given at 10–30 mg, titrated weekly by 10 mg

Sertraline and SSRI/antidepressant and Duration: 6 months psychoeducation other psychotherapy Frequency: psychoeducation weekly, sertraline daily

Dose/length of sessions: 10 sessions of psychoeducation, length NR

Franćišković et al. Tianeptine and group Antidepressant and Duration: 6 months Face to face; setting NR; psychiatrist (2011)80 therapy other psychotherapy and psychologist with mental health Frequency: group therapy twice weekly, backgrounds tianeptine daily Drugs prescribed by physician Dose/length of sessions: 37.5 mg/day, NR for group therapy

Fluoxetine and group SSRI/antidepressant and Duration: 6 months therapy other psychotherapy Frequency: group therapy twice weekly, fluoxetine daily

Dose/length of sessions: 40 mg/day, NR for group therapy erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) Intervention categories Control(s) strength of dose/length of sessions) professional)

Kosten et al. Phenelzine and Antidepressant and Placebo and Duration: NR Face to face; setting NR; master’s-level (1992)97 psychotherapy TFCBT psychotherapy psychologist with mental health Frequency: psychotherapy weekly, background. Drug delivery NR imipramine daily

Dose/length of sessions: dose of drug and length of sessions NR. Mean maximal dose 68 ± 20 mg Imipramine and Antidepressant and Duration: NR psychotherapy TFCBT Frequency: psychotherapy weekly, imipramine daily tal. et elhTcnlg seset2020 Assessment Technology Health Dose/length of sessions: dose of drug and ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under length of sessions NR. Mean maximal dose 225 ± 55 mg

Otto et al. (2003)116 CBT and sertraline SSRI/antidepressant and Compared Duration: NR Face to face; otherwise NR. Drug TFCBT with SSRI/ delivery NR antidepressant; Frequency: CBT NR, sertraline daily see Table 29 Dose/length of sessions: CBT 10 sessions, length NR

Sertraline initiated at 25 mg, titrated by 50 mg each week to a maximum of 200 mg. Mean final dose 100 mg/day continued o.2 o 43 No. 24 Vol. 209 210 PEDX4 APPENDIX IRJunl Library Journals NIHR www.journalslibrary.nihr.ac.uk

TABLE 30 Intervention characteristics for randomised controlled studies included comparing combined psychological and pharmacological interventions (continued)

Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) Intervention categories Control(s) strength of dose/length of sessions) professional)

Rothbaum et al. D-cycloserine and virtual D-cycloserine and Placebo and Duration: 6 weeks Face to face; setting NR; doctoral-level (2014)129 reality exposure therapy TFCBT exposure therapy clinicians with a mental health Frequency: weekly background. Drug delivery supervised within sessions Dose/length of sessions: introductory session, five therapeutic sessions, 90 minutes each

D-cycloserine delivered at 50 mg 30 minutes before exposure

Alprazolam and virtual Benzodiazepine and Duration: 6 weeks reality exposure therapy TFCBT Frequency: weekly

Dose/length of sessions: introductory session, five therapeutic sessions, 90 minutes each

Alprazolam delivered at 0.25 mg 30 minutes before exposure erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Intensity (duration, frequency and Delivery (method, setting and type of Authors (year) Intervention(s) Intervention categories Control(s) strength of dose/length of sessions) professional)

Sonne et al. Venlafaxine and CBT Antidepressant and Duration: 20–24 weeks Face to face; psychiatry centre; (2016)134 TFCBT psychiatrist Frequency: venlafaxine daily, CBT weekly

Dose/length of sessions: 10 sessions with a psychiatrist, 16 sessions with a psychologist

Venlafaxine initiated at 37.5–75 mg/day, increased weekly by 37.5–75 mg for 6 weeks. Rest of trial, monthly increases up to a maximum of 375 mg tal. et elhTcnlg seset2020 Assessment Technology Health Sertraline and CBT SSRI/antidepressant and Duration: 20–24 weeks ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under TFCBT Frequency: venlafaxine daily, CBT weekly

Dose/length of sessions: 10 sessions with a psychiatrist, 16 sessions with a psychologist

Sertraline initiated at 25–50 mg/day, increased weekly by 25–50 mg for 6 weeks. Rest of trial, monthly increases up to a maximum of 200 mg TFCBT, trauma-focused CBT. o.2 o 43 No. 24 Vol. 211

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 5 Population characteristics of included randomised controlled trials

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 213 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. 214 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included

Trauma

www.journalslibrary.nihr.ac.uk experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Acarturk et al. Refugee Turkey/Syria I = 35.27 (13.21), C = 37.92 (9.06) 24.14 NR NR NR No (2015)53

Acarturk et al. Refugee Turkey/Syria I = 33.32, C = 34.04 26 NR Syrian refugees (100%) NR Yes (2016)54

Adenauer et al. Refugee Germany I = 30.3 (9.2), C = 36.4 (9.9) I = 56.3, C = 55.6 I = Middle East (50%), Refugees and asylum seekers Unclear (mention of Yes (100%) (2011)55 Central East (13%), (100%) depression) Africa (38%)

C = Middle East (61%), Central East (6%), The Balkans (17%), Africa (11%)

Rezaei Ardani Veterans Iran I = 50.08 (4.5), Placebo = 51.5 (6.4), 100 NR Veterans of the Iraq–Iran war NR Yes (100%) et al. (2017)56 No intervention = 49.08 (6.13) (100%)

Azad Marzabadi War affected Iran Range: I = 35–45 (57.1%), 100 NR War victims from the NR and Hashemi 46–55 (35.8%), 56–60 (7.1%); Iran–Iraq war Zadeh (2014)57 C = 35–45 (35.7%), 46–55 (64.3%)

Bartzokis et al. Veteran USA 51.6 (4.2) 100 White (n = 44), Veterans NR Yes (2005)58 African American (n = 19), other (n = 2)

Becker et al. Veteran USA 50.39 (7.46) 79 African American (64%), War trauma (50%), domestic NR Yes (2007)59 white (29%), other (7%) violence (7%), rape (3.5%), motor vehicle accident (7%), homicide (7%), medical illness (11%), death/suicide of a loved one (7%), childhood sexual or physical abuse (7%)

Beidel et al. Veteran USA I = 58.93, C = 59.76 100 White (100%) Veterans (100%) NR Yes (100%) (2011)60

Bichescu et al. War affected Romania I = 68.9 (4.4), C = 69.8 (6.0) I = 100, C = 88.9 NR Former political detainees NR Yes (100%) (2007)61 (100%) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: Trauma experience Type(s) of trauma Current PTSD diagnosis at rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Bolton et al. War affected Iraqi BADT = 36.9 (12.4), CPT = 41.5 BADT = 43, NR Victims of systematic violence Depression: 100% NR (2014)62 Kurdistan (13.7), C = 42.3 (12.5) CPT = 42, C = 41 (including physical torture, (was a necessary imprisonment, gas attacks, condition of other military attacks) inclusion)

Buhmann et al. Refugee Denmark Medication + psychoeducation + 59 NR Refugees (including those Of completers (217), Yes (2016)63 CBT = 45 (10), medication + who had experienced torture, 94% had depression, psychoeducation = 43 (9), a refugee camp/asylum centre 27% had a CBT = 46 (8), waitlist = 47 (8) or were an ex-combatant) personality change (ICD-10 code F62.0), 9% were psychotic and 36% were in treatment for somatic disorder. About one-third reported a traumatic brain injury

Carlson et al. Veteran USA EMDR = 52.7 (8.6), RXT = 46.9 (4.0), 100 EMDR = white (60%), Veterans (100%) NR Yes (100%) (1997)64 C = 45.4 (3.5) RXT = white (54%), C = white (50%) tal. et Celik et al. Veteran Turkey I = 32.5 (4.7), C = 29.1 (7.4) NR NR Veterans (100%) On average, both Yes 2020 Assessment Technology Health (2011)65 groups met the cut- ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under off for depression and anxiety based on baseline scores

Chard (2005)66 Childhood USA 32.77 (8.87) 0 African American (14%), Childhood sexual abuse Current major Yes (100%) sexual abuse white (81.4%), Hispanic, (100%) depression (40%) Latin or Mexican (3.5%), other (1%)

Chung et al. Veteran South Korea I = 59.1 (6.04), C = 60.59 (6.70) 100 NR Veterans (100%) Major depressive Yes (2004)67 disorder: I = 11 (21.6%), C = 6 (14.3%)

Dysthymia: I = 37 (72.6%), C = 42

(81.6%) 43 No. 24 Vol.

Major depressive disorder and dysthymia: I = 3 (6.1%), C = 1 (2.04%) continued 215 216 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

Trauma experience Type(s) of trauma Current PTSD diagnosis at www.journalslibrary.nihr.ac.uk Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Classen et al. Childhood USA 38.4 (11.7) 0 White/European American Childhood sexual abuse NR Yes (2001)68 sexual abuse (64%), Hispanic/Latina (100%) (15%), black/African American (8%), native American (4%), other (10%)

Cloitre et al. Childhood USA 34 (7.22) 0 White (46%), African Childhood sexual/physical Major depression Yes (100%) (2002)69 sexual abuse American (20%), Hispanic abuse (100%): sexual and (45%), anxiety (15%), other (19%) physical abuse (48%), sexual disorders (79%), abuse (39%), physical abuse generalised anxiety (13%) disorder (48%)

Cloitre et al. Childhood USA STAIR/expsoure = 33.2, STAIR/ 0 STAIR/support = Childhood abuse (100%). Axis I diagnosis: Yes (100%) (2010)70 sexual abuse support = 37.1, support/ white (33–37%), African The large majority also STAIR/support = exposure = 38.7 American (24%), Hispanic experienced interpersonal 84.8%, STAIR/ (30%), other (9%) abuse as adults (including exposure = 92.1%, domestic violence, sexual support/exposure = STAIR/exposure = abuse and other interpersonal 87.9% white (37%), African abuse) American (21%), Hispanic Axis II diagnosis: (29%), other (11%) STAIR/support = 48.5%, STAIR/ Support/exposure = exposure = 52.6%, white (33%), African support/exposure = American (39%), Hispanic 60.6% (18%), other (9%)

Cook et al. Veteran USA I = 59.79 (3.18), C = 59.06 (3.86) 100 I = white (44.3%), African Vietnam veterans (100%) I = depressive Yes (100%) (2010)71 American (49.2%), other disorder (57.4%), (6.6%) anxiety disorder (57.4%) C = white (39.7%), African American (54%), C = depressive other (6.4%) disorder (55.6%), anxiety disorder (49.2%) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Davis et al. Veteran USA I = 53.8 (8.7), C = 53.8 (7.1) 97.6 I = white (54%), African Combat (97.6%), sexual I = major depression Yes (100%) (2004)73 American (46%) trauma (2.4%) (42%), dysthymia (27%), panic with C = white (53%), African I = combat (96%), sexual agoraphobia (4%) American (47%) trauma (4%) C = major depression C = combat (100%), sexual (40%), dysthymia trauma (0%) (27%), panic without agoraphobia (13%)

Davis et al. Veteran USA 55.2 (6.8) 98 NR Combat-related trauma (95%) NR Yes (100%) (2008)72

Devilly et al. Veteran USA 50.1 (6.48) 100 NR Veterans (100%) NR Yes (100%) (1998)74

Edmond et al. Childhood USA 35; follow-up = 36 (range 18–51) 0 White (85%), follow- Childhood sexual abuse: NR NR (1999);76 sexual abuse up = 83% 100%, childhood physical Edmond and abuse 58%, adult re- Rubin (2004)75 victimisation (including tal. et elhTcnlg seset2020 Assessment Technology Health domestic violence and

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under rape 66%)

Engel et al. Veteran USA I = 36.2 (7.75), C = 36.7 (9.75) I = 79.1, C = 83.8 I = white, not Hispanic Recently deployed military NR Yes (100%) (2015)78 (53.5%) service members and veterans C = white, not Hispanic (56.8%)

Feske (2008)79 Mixed USA 43.1 (range 29–55) 0 African American (95.2%), Multiple traumas (100%), Current comorbid Yes (100%) white (4.8%) including childhood sexual Axis-I (95.2%) abuse (85.7%) [including major depression (66.7%), Index traumas: adult sexual panic disorder assault (47.6%), domestic (38.1%), social violence (23.8%), child sexual phobia (28.6%), abuse (19%), child physical generalised anxiety abuse (4.8%), witnessed disorder (23.8%), murder (4.8%) borderline 43 No. 24 Vol. personality disorder (52.4%)] continued 217 218 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

Trauma experience Type(s) of trauma Current PTSD diagnosis at

www.journalslibrary.nihr.ac.uk Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Franćišković Mixed Croatia Median = 48 (range 37–60) 100 NR Veterans with combat NR Yes (100%) et al. (2011)80 experience from the Homeland War in Croatia (100%), torture and imprisonment (9.3%), refugees (6.9%)

Franklin et al. Veteran USA 46.1 (15.5) 92.6 Euro-American (69.2%), Veterans (7.4% reported NR Yes (100%) (2017)81 African American (23.1%), as having no war zone ‘other’ (7.7%) experience)

Friedman et al. Veteran USA I = 45, C = 46 I = 79, C = 81 White: I = 67%, C = 75% Primary exposure: being in Major depression: Yes (2007)82 war or combat (I = men I = men (50%), 85.3%, women 11.1%; women (56%); C = men 88.1%, women 6.3%), C = men (40%), physical or sexual assault women (56%) (I = men 2.9%, women 66.7%; C = men 3%, women 62.5%) Anxiety disorder: I = men (22%), women (22%); C = men (13%) women (25%)

Gamito et al. Veteran Portugal NR 100 Unclear Veterans of Portuguese NR Yes (100%) (2010)83 Colonial War (100%)

Germain et al. Veteran USA BSI = 40 (14.1), prazosin = 39.4 BSI = 82.4, Caucasian: BSI = 70.6%, Veterans of various wars BSI = generalised Yes (BSI = 41.2%, (2012)84 (11.9), C = 43.6 (14.0) prazosin = 88.9, prazosin = 83.3%, (100%) anxiety disorder prazosin = 72.2%, placebo = 100 placebo = 93.3% (5.9%), major placebo = 60%) depressive disorder (5.9%), insomnia (41.2%)

Prazosin = generalised anxiety disorder (5.6%), insomnia (16.7%)

Placebo = insomnia (33.3%) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Hamner et al. Veteran USA I = 50.8 (4.9), C = 53.7 (7.6) 100 I = white (53%), African Veterans of the Vietnam war Major depressive Yes (2003)85 American (47%) episodes 86%, other anxiety disorder C = white (39%), African 41%, number of American (61%) psychotic symptoms: I = 3.7 (SD 1.6), C = 4.1 (SD 0.9)

Hermenau et al. War affected Democratic 19 (2.02) 100 NR Former child soldiers and NR NR (2013)86 Republic of ex-combatants the Congo

Hijazi et al. Refugee USA 48.2 (8.9) 44.4 Iraqi (100%) Oppressed because of race/ NR Yes (2014)87 ethnicity/religion (92.1%), combat exposure (92.1%), witnessed destruction of religious shrines (74.6%), witnessed murder (68.3%), tal. et witnessed someone physically 2020 Assessment Technology Health harmed (66.7%), property ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under looted/confiscated/destroyed (65.1%), murder/violent death of family or friends (65.1%), witnessed rotten corpses (60.3%), kidnapping of family/ friends (58.7%), witnessed arrest/torture/execution of religious leaders (46%), witnessed torture (41.3%), physically harmed (38.1%), imprisoned arbitrarily (28.6%), witnessed mass execution (27%), kidnapped (27%), tortured (25.4%), serious physical injury from combat/ mine (25.4%), taken hostage (17.5%), sexually abused/ 43 No. 24 Vol. raped (6.3%) continued 219 220 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

Trauma www.journalslibrary.nihr.ac.uk experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Himmerich et al. Veteran Germany I = 29 (7.62), C = 28.8 (3.4) 100 NR Soldiers (100%) NR NR (2016)88

Hinton et al. Refugee USA NR I = 50, C = 50 Vietnamese (100%) Refugees (100%). All men NR Yes (100%) (2004)90 were ex-political detainees (former Southern Vietnamese military, police or political officials imprisoned by Northern Vietnamese)

Hinton et al. Refugee USA I = 50.9 (6.11), C = 52.7 (7.43) I = 40, C = 40 Cambodian refugees Cambodian refugees living in NR Yes (100%) (2005)89 the USA (100%)

Jensen (1994)91 Veteran USA 43.1 (2.84) 100 NR Veterans 40% had received a Yes recent veteran’s affairs diagnosis of alcohol abuse or alcohol dependence, but owing to 88% of subjects being in current receipt of inpatient, outpatient or domiciliary services, subjects were considered to not have ingested alcohol or other non-prescribed drugs during the study

Jung and Steil Childhood Germany 37.18 (range: 19–61) 0 Total sample: white (89%), Childhood sexual abuse Major depressive Yes (2013)92 sexual abuse Asian (11%) (100%) disorder (57.1%), eating disorders (32.1%), borderline personality disorder (32.1%) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Katz et al. Mixed USA HR = 45, PE = 36, C = 42 0 HR = white (41%), African Sexual trauma history: NR Yes (100%) (2014)93 American (24%), Hispanic veterans (100%) (6%), other/missing data (29%) Military sexual trauma (HR = 82%, PE = 82%, PE = white (41%), African PC = 94%) American (12%), Hispanic (12%), other/missing data Domestic violence (HR = 76%, (35%) PE = 71%, C = 65%)

C (control) = white (47%), Child abuse (HR = 100%, African American (24%), PE = 59%, C = 82%) Hispanic (17%), other/ missing data (12%) Adult abuse (HR = 71%, PE = 47%, C = 41%) tal. et Keane et al. Veteran USA I = 34.7 (4.3), C = 34.5 (2.1) 100 I = white (91%), Veterans NR Yes 2020 Assessment Technology Health (1989)94 Hispanic (9%) ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under

C = white (69%), black (31%)

Kearney et al. Veteran USA I = 52 (13.4), C = 52 (11.7) 79 I = white (76%), African Veterans NR Yes (2013)95 American (20%)

C = white (59%), African American (9%), other (27%)

Knaevelsrud War affected Iraq/ 28.1 (7.43) 28 Iraqi War related (including bomb Depression, anxiety Yes et al. (2015)96 Germany attacks and torture) and (remote) sexual abuse

Kosten et al. Veteran USA 39 (2.3) 100 Non-white (12%) Vietnam veterans with PTSD Minor depression Yes (100%) (1992)97 (100%) (47.4%) o.2 o 43 No. 24 Vol. continued 221 222 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

Krupnick et al. Childhood USA 32.1 (10.2) 0 African American (75%), I = mean of 6.8 (SD = 4.2), NR Yes (100%) (2008)98 sexual abuse Hispanic black (4.2%), different types of Afro-Caribbean (2.1%), interpersonal traumas Latina (8.3%), non- Hispanic white (6.2%), C = mean of 5.7 (SD = 3.5), Asian American (4.2%) different types of interpersonal traumas

Sexual trauma (97.1%, of which 97.9% were before 12 years of age), physical assault before 12 years of age (95.9%)

Krystal et al. Veteran USA I = 54.2 (10.8), C = 54.5 (10.6) 96.6 Means (SD) Combat trauma (78.3%) NR Yes (2011)99 White (not Hispanic): I = 84 (63.2), C = 93 (69.4)

Black (not Hispanic): I = 25 (18.8), C = 25 (18.7)

Hispanic: I = 16 (12.0), C = 11 (8.2)

Other: I = 8 (6), C = 5 (3.7)

Kubany et al. Domestic USA 36.4 (9.1) 0 White (n = 18), Asian Battered women (physical NR Yes (2003)100 violence (n = 10), Pacific Islander domestic abuse) (n = 6), black and Puerto Rican (n = 3)

Kubany et al. Domestic USA 42.2 (10.1) 0 White (52.8%), Native All physically, sexually and/or NR Yes (100%) (2004)101 violence Hawaiian (8.8%), Filipino psychologically abused by (7.2%), Japanese (6.4%), intimate romantic partner. black (4.8%), Samoan Physically hurt more than five (4.8%), American Indian times (68%), physically hurt (1.6%), other or mixed by more than one intimate ethnicity (13.6%) partner (51%) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Lande et al. Veteran USA Range: 18–25 (35.9%), 26–35 85 NR Veterans NR Yes (2010)102 (33.3%), ≥ 36 (30.7%)

Lau and Childhood Denmark I = 34.2 (10.5), C = 32.4 (8.8) 0 NR Childhood sexual abuse Females aged 30–39 Yes: I = 16%, Kristensen sexual abuse (intrafamilial) years: affective C = 29% (2007);103 Elkjaer disorders et al. (2014)77 Females aged 40–41 years: anxiety disorders

Females aged 42 and 44–49 years: other nervous diseases tal. et Females aged 50–59 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under years: behavioural syndromes

Females aged 60–62 years: personality disorders

Lindley et al. Veteran USA I = 52.9 (0.7), C = 53.9 (0.4) 100 White (62.5%), African Veterans (100%) Most patients had Yes (100%) (2007)104 American (17.5%), comorbid depression Hispanic (16%), other (5%)

Margolies et al. Veteran USA I = 36.43 (9.3), C = 39.11 (8.9) I = 90, C = 90 I = white (40%), Operation Enduring Freedom/ NR Yes (100%) (2011)105 black (60%) Operation Iraqi Freedom veterans C = white (40%), black (60%)

continued 43 No. 24 Vol. 223 224 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued) www.journalslibrary.nihr.ac.uk Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

McDonagh et al. Childhood USA CBT = 39.8 (9.9), PCT = 39.6 (9.6), 0 CBT = white (90%), Childhood sexual abuse NR Yes (100%) (2005)106 sexual abuse C = 42 (9.8) African American (0%), (100%), characteristics: Native American (10%), other (0%) CBT = life threat (34.5%), injured (41.4%), penetrated PCT = white (95%), (72.4%), mean age at African American (5%), onset = 6.1(2) Native American (0%), other (0%) PCT = life threat (5%), injured (31.8%), penetrated (59.1%), Waitlist = white (96%), mean age at onset = 7.6(2.8) African American (0%), Native American (0%), Waitlist = life threat (26.1%), other (4%) injured (27.3%), penetrated (56.5%), mean age at onset = 6.1(2.9)

CBT = childhood physical abuse (82.8%), adult physical abuse (58.6%), adult sexual trauma (44.8%), mean number of trauma types = 3.3 (1)

PCT = childhood physical abuse (81.8%), adult physical abuse (68.2%), adult sexual trauma (63.6%), mean number of trauma types = 3.1 (1.3)

Waitlist = childhood physical abuse (73.9%), adult physical abuse (60.9%), adult sexual trauma (43.5%), mean number of trauma types = 3.4 (0.9) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

McLay et al. Veteran USA I = 28 (range: 22–43), C = 28.8 I = 90, C = 100 NR Active duty service members NR Yes (100%) (2011)107 (range: 21–45) with PTSD (100%)

I = shot (10%), ambush (20%), improvised explosive device blast (20%), mortar attack (20%), suicide bomber (10%), firefight (10%), military medical trauma (10%)

C = improvised explosive device blast (30%), close combat (10%), firefight (20%), suicide bomber (10%), civilian casualties (20%), bridge collapse (10%)

Meffert et al. Refugee Egypt I = 31.3, C = 30.4 19 Sudanese Refugees (no further detail) NR Yes tal. et (2014)108 2020 Assessment Technology Health ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Miyahira et al. War affected USA NR NR NR Returning war fighters from NR Yes (2012)109 Iraq or Afghanistan

Monnelly et al. Veteran USA I = 48.9 (8.3), C = 53.5 (3.0) 100 White (80%), black Combat (100%) I = major depression Yes (100%) (2003)110 (13.3%), Hispanic (6.7%) (26.7%), dysthymic disorder (6.7%), generalised anxiety disorder (13.3%), panic disorder (6.7%)

C = major depression (40%), dysthymia (6.7%), generalised anxiety disorder (6.7%)

Moradi et al. Veteran Iran I = 45.25 (3.86), C = 45.33 (3.80) 100 Iranian War trauma (mixed) NR Yes 43 No. 24 Vol. (2014)111 continued 225 226 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

www.journalslibrary.nihr.ac.uk Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Naylor et al. Veteran USA I = 39.21 (4.7), C = 35.86 (9.69) NR NR Combat-related (41.6%), C = obsessive Yes (partial (2013)112 non-combat related with a compulsive disorder, PTSD = 100%) history of combat (41.6%) and generalised anxiety non-combat related with no disorder and combat experience (16.7%) agoraphobia (8.3%), major depressive episode (8.3%), agoraphobia (8.3%)

Neuner et al. Refugee Uganda NET = 31.9 (6.7), supportive 37 Sudanese Refugees (including those NR Yes (2004)114 counselling = 33.8 (7.9), who had witnessed killings psychoeducation = 34.2 (6.9) and experienced torture)

Neuner et al. Refugee Uganda NET = 34.4 (12.2), trauma 48.7 Somalian (45.1%), 13.1–14.5 types of traumatic NR NR (2008)113 counselling = 35.2 (12.8), Rwandan (54.9%) events in groups. Majority of C = 35.6 (14.0) the refugees in Nakivale fled civil conflict

Niles et al. Veteran USA 52.0 (13.0) 100 White, not Hispanic Veterans NR Yes (2012)115 (76%, n = 25), black, not Hispanic (15%, n = 5), white, Hispanic (6%, n = 2) and ‘other’ (3%, n = 1)

Otto et al. Refugee USA 47.2 0 Cambodian (100%) Refugees (100%) High unreported Yes (100%) (2003)116 psychiatric comorbidity

Owens et al. Childhood USA 33 (9.15) 0 African American (11%), Childhood sexual abuse NR Yes (100%) (2001)117 sexual abuse white (87%), Hispanic/ (100%). Sexual abuse events Latino/Mexican American reported: vaginal and/or anal (2%) penetration, kissing, fondling and oral sexual contact

Panahi et al. Veteran Iran I = 46.5 (5.4), C = 44.6 (5.1) 100 NR Iranian Iran–Iraq war NR Yes (100%) (2011)118 veterans (100%) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: Trauma experience Type(s) of trauma Current PTSD diagnosis at rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Paunovic and Refugee Sweden 37.9 (7.6) 85 NR Refugees (100%). Experienced NR Yes (100%) Ost (2001)119 more than one traumatic event (70%). Primary traumatic events (assumed to be based on 16 completers): torture = 6, combat = 6, physical assault in civilian life = 5, witnessing murder of significant others = 4, witnessing massacre = 3, assault with weapon in civilian life = 2, transportation accident = 2, witnessing physical assault in civilian life = 2, witnessing assault with weapon in civilian life = 2, witnessing sudden violent death = 2, witnessing murder of strangers = 2, death threats against family = 2, threat of torture = 1, sexual assault = 1, tal. et exposure to toxic 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under substance = 1, death threats with a weapon in civilian life = 1

Polusny et al. Veteran USA I = 57.6 (10.4), C = 59.4 (9.2) MBSR = 79, MBSR = white (81%), Veterans (100%), lifetime I = mood disorder Yes (full (2015)120 PCT = 90 black (5%), other (4%), traumas: (44.8%) PTSD = 97.4%, mixed (10%) subthreshold I = combat exposure (68%), C = mood disorder PTSD = 2.6%). PCT = white (86%), sexual trauma (37%), physical (39.7%) Per group: full black (10%), other (4%), assault (68%), disaster PTSD (I = 98.3%, mixed (0%) exposure (44%), serious injury No other C = 96.6%), event (67%), life-threatening comorbidities subthreshold PTSD illness/injury (60%), other reported as (I = 1.7%, C = 3.4%) (97%) measured

C = combat exposure (80%), sexual trauma (19%), physical o.2 o 43 No. 24 Vol. assault (63%), disaster exposure (43%), serious injury event (61%), life-threatening illness/injury (56%), other (93%) continued 227 228 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no) www.journalslibrary.nihr.ac.uk Possemato et al. Veteran USA I = 46.3 (16.4), C = 47.4 (16.2) 87.1 White (82.3%) Veterans NR Yes (48.4%) (2016)121

Raskind et al. Veteran USA 56 (9) 95 White (n = 26), African Veterans Depression Yes (2007)122 American (n = 11), Asian American (n = 1), Hispanic (n = 1) and Native American (n = 1)

Overall (40)

Raskind et al. Veteran USA I = 30.0 (6.6), C = 30.8 (6.5) I = 81, C = 89 I = African American Active duty soldiers returned I = major depression Yes (100%) (2013)123 (13%), Asian (3%), from Afghanistan and Iraq (34%), C = major Caucasian (66%), Hispanic (100%) depression (43%) (16%), other (3%) I = mean number of C = African American deployments 2.6 (SD 4.0), (14%), Caucasian (60%), combat experiences scale Hispanic (9%), Native score 10.9 (SD 3.8) American (6%), other (11%) C = mean number of deployments 1.9 (SD 1.2), combat experiences scale score 11.9 (SD 3.6)

Ready et al. Veteran USA Virtual reality exposure = 57 (range: 100 White (54.5%), African Vietnam veterans NR Yes (100%) (2010)124 53–61), PCT = 58 (range: 55–62) American (45.5%)

Reed and Domestic USA 44.95 (7.01) 100 European Americans Romantic partner emotional NR NR Enright (2006)125 violence (90%), Hispanic American abuse: criticising (90%), (5%), Native American ridiculing (100%), jealous (5%) control (75%), purposeful ignoring (100%), threats of abandonment (25%), threats of personal harm (30%), threats of harm to property or pets (20%), sexual abuse (30%: n = 5 ridicule followed by demands for sexual favours, n = 1 threats of physical harm combined with demands for sexual favours) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI:

Trauma rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Reger et al. Veteran USA Virtual reality exposure = 29.52 > 95 White (59.9%), black Veterans NR Yes (2016)126 (6.47), PE = 30.89 (7.09), (9.3%), Hispanic (17.3%) C = 30.39 (6.45)

Reich et al. Childhood USA I = 30.6, C = 24.2 0 White: I = 75%, C = 100% Trauma related to childhood: Major depression Yes (2004)127 sexual abuse emotional (I = 66.7%, (I = 66.6%, African American: C = 54.5%), verbal (I = 50%, C = 55.5%) I = 16.7%, C = 0% C = 77.8%), physical (I = 50%, C = 44.4%), sexual abuse Dysthymia (I = 8.3%, Asian American: I = 8.3%, (I = 83.3%, C = 66.7%) C = 0%) C = 0% Panic disorder (I = 25%, C = 11.1%)

Agoraphobia with panic disorder (I = 16.6%, C = 0%)

Agoraphobia without panic disorder (I = 8.3%, C = 0%) tal. et elhTcnlg seset2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Generalised anxiety disorder (I = 8.3%, C = 22.2%)

Simple phobia (I = 25%, C = 0%)

Social phobia (I = 0%, C = 11.1%)

Eating disorder not otherwise specified (I = 8.3%, C = 0%)

Obsessive– compulsive disorder = =

(I 0%, C 11.1%) 43 No. 24 Vol.

Somatisation disorder (I = 8.3%, C = 0%) continued 229 230 PEDX5 APPENDIX IRJunl Library Journals NIHR www.journalslibrary.nihr.ac.uk TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Resick et al. Veteran USA I = 31.8 (7.3), C = 32.4 (7.9) CPT-C = 93, CPT-C = black (20%), Active duty military with NR Yes (100%) (2015)128 PCT = 92 Hispanic (9%), white criterion A traumatic event (63%), other (9%) (100%)

PCT = black (21%), Hispanic (19%), white (52%), other (8%)

Rogers et al. Veteran USA Range: 47–53 100 NR Vietnam veterans (100%) NR Yes (100%) (1999)130

Rothbaum et al. Veteran USA D-cycloserine + PE = 34.9, 95 Black (50.6%), white Veterans 27.5% had a Yes (2014)129 alprazolam + PE = 36.2, C = 34.3 (41.6%), Hispanic (5%) comorbid mood disorder

Sikkema et al. Childhood USA Female = 43.18 (6.99), male = 41.75 46 Total sample: white Primarily childhood sexual HIV-positive sero- Yes (2007)131 sexual abuse (6.99) (11.3%), African American abuse. 62% of women and status; meets DSM- (68.6%), Hispanic-Latino 43% of men also experienced IV criteria for PTSD: (16%), other (4.1%) rape as adults women (37%), men (43%)

Sikkema et al. Childhood USA 42.3 (6.8) 47 Overall: African American Childhood sexual abuse NR Yes (40%) (2013)132 sexual abuse (68%), Hispanic (17%), white (10%)

Smajkic et al. Refugee USA 51.34 (10.11) Venlafaxine = 100, Bosnian (100%) Refugees (100%) NR Yes (100%) (2001)133 sertraline = 40, paroxetine = 25 erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Sonne et al. Refugee Denmark I = 43.2 (9.6), C = 44 (9.7) Venlafaxine = Origin: venlafaxine = Refugees (100%): Venlafaxine = Yes (100%) (2016)134 62.2, sertraline = ex-Yugoslavia (11.2%), venlafaxine = depression (97.96%), 58.3 Iran (13.3%), Iraq (34.7%), imprisonment (58.8%), torture enduring personality Afghanistan (10.2%), (55.1%), refugee camp change after Lebanon (12.6%), other (22.9%); sertraline = catastrophic (18.4%); sertraline = imprisonment (48.6%), torture experience (41.3%), ex-Yugoslavia (8.3%), Iran (41.7%), refugee camp other psychiatric (13.9%), Iraq (34.4%), (27.5%) disorder (12.24%); Afghanistan (16.7%), sertraline = Lebanon (13%), other depression (99.08%), (13.9%) enduring personality change after catastrophic experience (40.38%), other psychiatric tal. et disorder (11.1%) 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Stein et al. Veteran USA I = 55.2 (6.6), C = 51.1 (8.1) 100 NR Military veterans (n = 3 All subjects had Yes (2002)135 Vietnam-related) depression and pronounced sleep problems

Stenmark et al. Refugee Germany I = 34.5 (11.1), C = 36.6 (11.0) I = 67, C = 73 Region of origin: Refugees and asylum seekers NR Yes (100%) (2013)136 I = Afghanistan (14%), with PTSD (100%). Mean Iraq (29%), Middle East number of traumatic events: (remaining countries) I = 8.3 (2.2), C = 7.9 (2.9) (16%), Africa (25%), other countries (16%); C = Afghanistan (17%), Iraq (23%), Middle East (remaining countries) (17%), Africa (26%), other countries (17%)

continued 43 No. 24 Vol. 231 232 PEDX5 APPENDIX IRJunl Library Journals NIHR

TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

Trauma experience Type(s) of trauma Current PTSD diagnosis at

www.journalslibrary.nihr.ac.uk Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Teng et al. Veteran USA I = 52.00 (8.13), C = 51.87 (9.07) 86 African American (42.9%), Veterans Panic disorder Yes (2008)137 white (42.9%), Hispanic (13.3%), panic (14.2%) disorder with agoraphobia (86.7%), specific phobia (23.3%), obsessive– compulsive disorder (13.3%), acute stress disorder (3.3%), generalised anxiety disorder (26.7%), major depressive disorder (60.0%), dysthymic disorder (30.0%)

Ter Heide et al. Refugee The I = 43.1 (10.7), C = 39.8 (11.9) 69 The vast majority of Refugees (including asylum 77.8% had comorbid Yes (2016)139 Netherlands refugees came from Iraq, seekers and illegal depression Afghanistan or countries immigrants) in Africa (ethnicities were NR). Other origin countries included Former Yugoslavia and other Middle-Eastern countries

Ter Heide et al. Refugee The I = 40 (9.31), C = 43 (7.93) I = 50, C = 70 Origin: Afghanistan (20%), Asylum seekers and refugees. Depression (I = 80%, NR (2011)138 Netherlands Algeria (5%), Bosnia Experienced 10 separate C = 50%) (20%), Iran (10%), Iraq events, on average, including: (30%), Lebanon (5%), murder/unnatural death of Turkey (5%) family or friend (95%), physical or psychological torture (70%)

Ulmer et al. Veteran USA I = 47.0 (9.5), C = 50.2 (11.6) I = 66.7, C = 55.6 I = African American Veterans with PTSD NR Yes (100%) (2011)140 (33.3%), white (33.3%), other (33.3%)

C = African American (33.3%), white (33.3%), other (33.3%) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

van der Kolk Mixed USA I = 40.8 (6.4), C = 39.9 (7.8) 30 NR 31/64 were veterans, 33 Depression (54.8%) Yes et al. (1994)141 were non-veterans (20/33 had experienced childhood sexual abuse)

Wahbeh et al. Veteran USA MM = 53.3 (12.6), SB = 52.2 (12.5), MM = 93, SB = 92, White (MM = 85%, Combat veterans with PTSD NR Yes (100%) (2016)142 MM + SB = 50 (12.8), SQ = 53 (11.8) MM + SB = 96, SB = 88%, (100%) SQ = 96 MM + SB = 88%, SQ = 84%) Combat exposure: MM = 24.1 (9.4), SB = 22.5 (8.5), MM + SB = 26.6 (10.3), SQ = 25.8 (9.8)

Lifetime trauma (Life Events

tal. et =

Checklist): MM 32.2 (7.8), 2020 Assessment Technology Health SB = 33.7 (5.7), ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under MM + SB = 32.7 (6.3), SQ = 31.3 (8.1)

Wang et al. War affected Kosovo I = 46.8 (10.4), C = 48.8 (10.9) 55 NR Victims of torture and war Depression = Yes (50%) (2016)143 (civilians) 92.9%, anxiety disorders = 89.3%

Weiss et al. War affected Iraq I = 41.6 (11.3), C = 45.16 (11.1) Male: I = (67.7), NR Survivors of systemic NR NR (2015), trial 1: C = (32.3) violence: having witnessed or CETA144 experienced physical torture or militant attacks

Weiss et al. War affected Iraq I = 40 (12.3), C = 41 (9.5) I = 67.4, C = 62.5 NR Survivors of systemic NR NR (2015), trial 2: violence: having witnessed or CPT144 experienced physical torture or militant attacks

continued 43 No. 24 Vol. 233 234 PEDX5 APPENDIX IRJunl Library Journals NIHR

www.journalslibrary.nihr.ac.uk TABLE 31 Population characteristics of the randomised studies of intervention effectiveness included (continued)

Trauma experience Type(s) of trauma Current PTSD diagnosis at Authors (year) category Country Age of males, years (SD) Gender (% male) Ethnicity experienced comorbidities baseline (yes/no)

Yeomans et al. War affected Burundi 38.6 (12.8) 65.6 Hutu (52.4%), Tutsi Witnessed: mixed (e.g. rape, NR NR (2010)145 (47.6%) serious injury owing to combat)

Experienced: combat (98.8%), forced to hide (97.1%), unnatural death of family member (96.7%), lack of food/water (95%), narrowly escaping death (91.7%), lack of shelter (90.4%), ill health without medical care (86.2%), loss of personal property (81.9%), confined indoors owing to danger (79.5%), betrayed and placed at risk of death (41.7%), serious physical injury from combat (35%), forced to hide among the dead (27.5%), imprisonment (23.8%); other

Zlotnick et al. Childhood USA 39 (9.59) 0 99% white (n = 1: Native Childhood sexual abuse Extreme stress Yes (1997)146 sexual abuse American) (100%)

Zohar et al. Veteran Israel I = 41 (6), C = 38 (9) I = 83, C = 95 NR Veterans (100%) NR Yes (100%) (2002)147 BATD, Behavioural Activation Treatment for Depression; BSI, Brief Symptom Inventory; CETA, common elements treatment approach; C, control; CPT, cognitive processing therapy; HR, holographic reprocessing; I, intervention; MM, mindfulness meditation; PCT, person-centred therapy; PE, prolonged exposure; RXT, relaxation; SB, slow breathing; SQ, sitting quietly. DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 6 Characteristics of included non-randomised controlled studies

TABLE 32 Characteristics of the interventions in the non-randomised controlled studies of intervention effectiveness included

Intensity (duration, frequency and strength of Delivery (method, setting and Authors (year) Intervention(s) Control(s) dose/length of sessions) type of professional)

King et al. Mindfulness-based Treatment as Duration: 8 weeks Face to face (group); outpatient (2013)148 cognitive therapy usual veterans’ affairs clinic; doctoral- Frequency: weekly and master’s-level clinicians with mental health backgrounds Dose/length of sessions: 8 hours

Unclear for treatment as usual group

Kruse et al. Trauma-focused Treatment as Duration: NR Face to face (individual); setting (2009)149 psychotherapy usual NR; trained psychotherapists Frequency: weekly (first 3 months), fortnightly (remainder)

Dose/length of sessions: 50 minutes, 25 hours total

Levi et al. CBT Duration: 24 weeks Face to face (individual); army (2016)150 PTSD treatment centre; Frequency: weekly psychiatrists, clinical psychologists and social workers Dose/length of sessions: NR

Psychodynamic Duration: 50 weeks psychotherapy Frequency: weekly

Dose/length of sessions: NR

Lundqvist et al. Group therapy Waitlist Duration: 2 years (phase 1, Face to face (group); hospital (2006)151 5 months; phase 2, 4 psychiatric outpatient unit; months; phase 3, 1 year) female group leaders, unknown training Frequency: twice a week (phase 1), weekly (phase 2), monthly (phase 3)

Dose/length of sessions: NR

Short-term Duration: 2 years (phase 1, focused therapy 5 months; phase 2, 4 months; phase 3, 1 year)

Frequency: twice a week (phase 1), weekly (phase 2), monthly (phase 3)

Dose/length of sessions: NR continued

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 235 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 6

TABLE 32 Characteristics of the interventions in the non-randomised controlled studies of intervention effectiveness included (continued)

Intensity (duration, frequency and strength of Delivery (method, setting and Authors (year) Intervention(s) Control(s) dose/length of sessions) type of professional) Morgan and Group No intervention Duration: 20 weeks Face to face (group); community Cummings psychotherapy social services; psychotherapists (1999)152 Frequency: weekly

Dose/length of sessions: NR

Narimani et al. EMDR Waitlist Duration: 70 days (typically) Face to face (individual); setting (2008)153 NR; trained therapists Frequency: NR

Dose/length of sessions: 90 minutes

CBT Duration: 70 days

Frequency: NR

Dose/length of sessions: 60–120 minutes Pivac et al. Olanzapine Duration: 6 weeks Drug intervention; delivered by (2004)154 hospital for PTSD; psychiatrists Frequency: once or twice daily

Dose/length of sessions: 5–10 mg

Fluphenazine Duration: 6 weeks

Frequency: once or twice daily

Dose/length of sessions: 5–10 mg

Salo et al. Individual therapy No intervention Duration: 1 year Face to face (individual); setting (2008)155 NR; master’s-level social Frequency: weekly workers and psychologists

Dose/length of sessions: NR

Group therapy Duration: 1 year Face to face (group); setting NR; therapists with a baccalaureate Frequency: weekly degree in psychology and social work with mental health Dose/length of sessions: NR backgrounds

Saxe and ‘Victim to survivor’ Waitlist Duration: 20 weeks Face to face (group); community Johnson group therapy mental health agency; (1999)156 Frequency: weekly experienced mental health social workers Dose/length of sessions: NR

236

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 7 Population characteristics of included non-randomised controlled studies

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 237 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. 238 PEDX7 APPENDIX IRJunl Library Journals NIHR

TABLE 33 Population characteristics of the non-randomised studies of intervention effectiveness included

Trauma PTSD experience Age of males, Gender diagnosis www.journalslibrary.nihr.ac.uk Authors (year) category Country years (SD) (% male) Ethnicity Type(s) of trauma experienced Current comorbidities at baseline? King et al. Veteran USA I = 60.1 (9.7), NR NR Veterans 65% of participants from the Yes (2013)148 C = 58.3 (8.3) treatment group and 76% from the control had a current major depressive disorder Kruse et al. Refugee Germany I = 44.7 (9.0), I = 35.3%, Bosnian Bosnian refugees (100%). Highly NR Yes (100%) (2009)149 C = 44.3 (12.2) C = 30% (100%) stressful war-related events:

I = close to death (97%), forced separation (82.3%), murder of family/ friends (70.6%), murder of strangers (67.7%), physical torture (70.6%), combat situation (50%), rape/sexual abuse (41.2%), brainwashed (85.3%), lack of food/water (67.7%), unnatural death of friends (58.8%), lost/ kidnapped (64.7%), lack of medical care (70.6%), no shelter (79.4%), imprisoned (55.9%), serious injury (70.6%), isolation (41.2%); number of events 10.7 (SD 4.4)

C = close to death (100%), forced separation (93.3%), murder of family/ friends (83.3%), murder of strangers (83.3%), physical torture (93.4%), combat situation (63.4%), rape/sexual abuse (50%), brainwashed (96.7%), lack of food/water (86.6%), unnatural death of friends (80%), lost/kidnapped (86.6%), lack of medical care (70%), no shelter (96.7%), imprisoned (80%), serious injury (90%), isolation (66.7%); number of events 13.5 (SD 3.2) erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI:

rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Trauma PTSD experience Age of males, Gender diagnosis Authors (year) category Country years (SD) (% male) Ethnicity Type(s) of trauma experienced Current comorbidities at baseline? Levi et al. Veteran Israel I = 30.8 (11.4), 100% NR Veterans NR Yes (2016)150 C = 33.4 (11.45) Lundqvist et al. Childhood Sweden Group therapy = 34 0% NR Childhood sexual abuse NR NR (2006)151 sexual abuse (range: 20–54), (100% female) short-term focused therapy = 39 (range: 25–54), C = 41 (range: 28–55) Morgan and Childhood Canada I = 36.92 (8.01), 0% NR Childhood sexual abuse NR NR Cummings sexual abuse C = 33.05 (10.27) (100% female) (1999)152

Narimani et al. War affected Iran Overall: 47.95 (5.07) NR Iranian Combatants afflicted and hospitalised NR NR (2008)153 (100%) at psychiatric/psychological hospital (100%)

Pivac et al. Veteran Croatia I = 37.2 (4.5), 100% NR Veterans All participants had comorbid Yes tal. et elhTcnlg seset2020 Assessment Technology Health (2004)154 C = 38.1 (4.8) psychotic symptoms: 37 (68%) ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under had psychotic depression with auditory hallucinations or auditory and visual hallucinations; 18 (37%) had delusional paranoid symptoms

Salo et al. War affected Palestine Individual 100% Palestinian Former political prisoners (100%). NR NR (2008)155 treatment = 32.36 (100%) Most common experiences of (1.44), group torture/ill treatment: different types treatment = 30.45 of beatings such as by gun or baton (1.40), C = 30.82 (87.8%), psychological abuse such (0.72) as sham execution (75.5%); classic torture methods less common: burning with cigarettes (13.8%), pain by electricity (11%)

Saxe and Childhood Canada NR 0% NR Childhood sexual abuse (incest) NR NR 43 No. 24 Vol. Johnson sexual abuse (100% female) (1999)156 C, control; I, intervention; SD, standard deviation. 239

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 8 Risk-of-bias gradings of included randomised controlled trials

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 241 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 8

Knaevelsrud 201596 +?–???+

Kosten 199297 +?????+

Krupnick 200898 ??–?+?+

Krystal 201199 +++++++

Kubany 2003100 ??–?–?–

Kubany 2004101 ?––+–?+

Lande 2010102 –––?–?+

Lau 2007103 +?+???+

Lindley 2007104 ? ?–+–?+

Margolies 2011105 ??–?–?+

McDonagh 2005106 ???+?–+ Random sequence generation (selection bias) Random sequence generation Allocation concealment (selection bias) Blinding of participants and personnel (performance bias) bias) Blinding of outcome assessment (detection Incomplete outcome data (attrition bias) reporting (reporting bias) Selective Other bias Acarturk 201553 +––+? ? ? McLay 2011107 –––––? ?

Acarturk 201654 +––++? ? Meffert 2014108 +––––?+

Adenauer 201155 +?–+––? Miyahira 2012109 ????–?+

Rezaei Ardani 201756 ?++?+–? Monnelly 2003110 ?????–+

Azad Marzabadi 201457 ????–?? Moradi 2014111 +???+?+

Bartzokis 200558 ??+?–?? Naylor 2013112 ??????+

Becker 200759 ??++??? Neuner 2004114 +–?++?+

Beidel 201160 ??–???? Neuner 2008113 ?––+–?+

Bichescu 200761 ??––??? Niles 2012115 ++–––?+

Bolton 201462 +?–++?? Otto 2003116 ??–?+–?

Buhmann 201663 ++–+++? Owens 2001117 ??–??–+

Carlson 199764 ??–???? Panahi 2011118 +?++??+

Celik 201165 ??––??? Paunovic 2001119 ??–?––+

Chard 200566 ?––+??? Polusny 2015120 +?––+++

Chung 200467 ????–?+ Possemato 2016121 +??++–+

Classen 200168 ?––?+?+ Raskind 2007122 ++++? ?+

Cloitre 200269 ?––?–?+ Raskind 2013123 ??++–?+

Cloitre 201070 ??–++?+ Ready 2010124 ??–+–?+

Cook 201071 +??++?+ Reed 2006125 ?????–+

Davis 200473 ??+???+ Reger 2016126 +??–+++

Davis 200872 ++++? ?+ Reich 2004127 ????+?+

Devilly 199874 ??––??+ Resick 2015128 ??–+–?+

Edmond 199976 ??–?+?+ Rogers 1999130 ??–++?+

Engel 201578 ++–++–+ Rothbaum 2014129 ? ?+++++

Feske 200877 ????–?+ Sikkema 2007131 ????+?+

Frančišković 201180 ????–?+ Sikkema 2013132 ????+?+

Franklin 201781 ??–+–?+ Smajkic 2001133 ????––+

Friedman 200782 +?+++?+ Sonne 2016134 ++–+?–+

Gamito 201083 ??–???+ Stein 2002135 ??++??+

Germain 201284 ????–?+ Stenmark 2013136 +?–+––+

Hamner 200385 ??+++?+ Teng 2008137 +–????+

Hermenau 201386 +??+–?+ Ter Heide 2011138 ?––?–?+

Hijazi 201487 ++––+?+ Ter Heide 2016139 +–? ?–++

Himmerich 201688 ??–???+ Ulmer 2011140 ??–?+?+

Hinton 200490 ??–???+ van der Kolk 1994141 ??+?–?+

Hinton 200589 +–?+?–+ Wahbeh 2016142 +?–+–?+

Jensen 199491 ?––?–?+ Wang 2016143 ++++–?+

Jung 201392 ????+?+ Weiss 2015144 +?–++–+

Katz 201493 ??–?–?+ Yeomans 2010145 +?–––?+

Keane 198994 ??––?–+ Zlotnick 1997146 ??–––?+

Kearney 201395 ?+–??++ Zohar 2002147 ????––+

FIGURE 26 Risk-of-bias ratings across the domains of the Cochrane tool for all included RCTs.

242

NIHR Journals Library www.journalslibrary.nihr.ac.uk DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 9 Summary tables of clinical effectiveness analyses

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 243 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. 244 PEDX9 APPENDIX IRJunl Library Journals NIHR Effectiveness of psychological interventions across all populations

Post-traumatic stress disorder outcomes

www.journalslibrary.nihr.ac.uk TABLE 34 Effectiveness of psychological interventions on PTSD outcomes for all trauma populations

Psychological Control Active control interventions vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

All SMD –0.90 (95% CI –1.14 to –0.66), SMD –0.45 (95% CI –0.82 to –0.08), SMD –0.35 (95% CI –0.72, 0.03), – I2 = 85.3%, number of trials = 39, n = 2506 I2 = 79.4%, number of trials = 10, n = 738 I2 = 47.0%, number of trials = 6, n = 259 Trauma-focused SMD –1.09 (95% CI –1.44 to –0.75), SMD –0.64 (95% CI –1.10 to –0.18), –– CBT I2 = 86%, number of trials = 21, n = 1283 I2 = 44.9%, number of trials = 4, n = 206

EMDR SMD –1.07 (95% CI –1.65 to –0.50), – SMD –0.15 (95% CI –0.62, 0.32), – I2 = 75.4%, number of trials = 7, n = 244 I2 = 0%, number of trials = 2, n = 71

IPT SMD –1.41 (95% CI –1.97 to –0.85), ––– I2 = 0%, number of trials = 2, n = 66

Mindfulness SMD –0.26 (95% CI –0.55, 0.04), SMD –0.08 (95% CI –0.68, 0.52), –– I2 = 0%, number of trials = 3, n = 183 I2 = 59%, number of trials = 2, n = 109

Non-trauma- SMD –0.05 (95% CI –0.23, 0.13), SMD –0.02 (95% CI –0.25, 0.20), –– focused CBT I2 = 0%, number of trials = 3, n = 548 I2 = 0%, number of trials = 2, n = 305

Single-component SMD –1.16 (95% CI –1.52 to –0.81), SMD –0.94 (95% CI –1.56 to –0.32), –– and trauma-focused I2 = 86.2%, number of trials = 23, n = 1264 I2 = 77.6%, number of trials = 5, n = 276 interventions

Multicomponent SMD –0.73 (95% CI –1.11 to –0.35), ––– and trauma-focused I2 = 62.3%, number of trials = 7, n = 385 interventions

Single-component SMD –0.39 (95% CI –0.66 to –0.12), SMD –0.05, (95% CI –0.23, 0.14), SMD –0.64 (95% CI –1.82, 0.53), – non-trauma-focused I2 = 69.6%, number of trials = 11, n = 936 I2 = 0%, number of trials = 5, n = 462 I2 = 76.9%, number of trials = 2, n = 62 interventions Phase-based Effect size –1.13 (95% CI –1.54 to –0.73), ––– interventions I2 = 35.9%, number of trials = 6, n = 190 erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: Complex post-traumatic stress disorder outcomes rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

TABLE 35 Effectiveness of psychological interventions on CPTSD outcomes for all trauma populations

Control Active control CPTSD symptom Psychological cluster interventions vs. control End of treatment Follow-up after < 6 months End of treatment Follow-up after < 6 months

Emotional All SMD –0.38 (95% CI –0.88 to 0.12), SMD –0.42 (95% CI –1.53 to 0.69), –– dysregulation I2 = 74.5%, number of trials = 7, n = 289 I2 = 72.3%, number of trials = 2, n = 51 Trauma-focused CBT SMD –0.17 (95% CI –0.82 to 0.49), SMD –0.42 (95% CI –1.53 to 0.69), –– I2 = 60.6%, number of trials = 3, n = 103 I2 = 72.3%, number of trials = 2, n = 51 Single-component and –––– trauma-focused interventions Multicomponent and trauma- –––– focused interventions Single-component and SMD –0.04 (95% CI –0.41 to 0.33), ––– non-trauma-focused I2 = 23.9%, number of trials = 4, n = 163 tal. et interventions 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Phase-based interventions SMD –0.76 (95% CI –1.79 to 0.27), ––– I2 = 83.4%, number of trials = 3, n = 118 Interpersonal All SMD –0.59 (95% CI –1.28 to 0.11), ––– problems I2 = 61.9%, number of trials = 2, n = 94 Trauma-focused CBT –––– Single-component and –––– trauma-focused interventions Multicomponent and trauma- –––– focused interventions Single-component and –––– non-trauma-focused

interventions 43 No. 24 Vol. Phase-based interventions SMD –0.59 (95% CI –1.28 to 0.11), ––– I2 = 61.9%, number of trials = 2, n = 94 continued 245 246 PEDX9 APPENDIX IRJunl Library Journals NIHR www.journalslibrary.nihr.ac.uk

TABLE 35 Effectiveness of psychological interventions on CPTSD outcomes for all trauma populations (continued)

Control Active control CPTSD symptom Psychological cluster interventions vs. control End of treatment Follow-up after < 6 months End of treatment Follow-up after < 6 months

Negative All SMD 1.81 (95% CI 0.73 to 2.89), ––– self-concept I2 = 90%, number of trials = 5, n = 215 Trauma-focused CBT SMD 2.22 (95% CI 0.75 to 3.70), ––– I2 = 90.4%, number of trials = 3, n = 145 Single-component and –––– trauma-focused interventions Multicomponent and trauma- SMD 2.93 (95% CI 2.40 to 3.45), ––– focused interventions I2 = 0%, number of trials = 2, n = 117 Single-component and SMD 1.14 (95% CI 0.01 to 2.27), ––– non-trauma-focused I2 = 72.6%, number of trials = 2, n = 70 interventions Phase-based interventions –––– erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Depression

TABLE 36 Effectiveness of psychological interventions on depression outcomes for all trauma populations

Control Active control

Psychological interventions Follow-up after vs. control Post treatment Follow-up after < 6 months Post treatment < 6 months

All SMD –0.89 (95% CI –1.15 to –0.64), SMD –0.51 (95% CI –0.80 to –0.22), SMD –0.32 (95% CI –1.23 to 0.59), – I2 = 81.3%, number of trials = 30, n = 1793 I2 = 48%, number of trials = 9, n = 410 I2 = 47.8%, number of trials = 2, n = 72 Trauma-focused CBT SMD –0.91 (95% CI –1.31 to –0.51), SMD –0.72 (95% CI –1.43 to –0.01), –– I2 = 87.3%, number of trials = 14, n = 1042 I2 = 56.6%, number of trials = 3, n = 104

EMDR SMD –1.12 (95% CI –1.68 to –0.55), – SMD –0.32 (95% CI –1.23 to 0.59), – I2 = 65.2%, number of trials = 5, n = 182 I2 = 47.8%, number of trials = 2, n = 72 tal. et IPT SMD –1.17 (95% CI –1.71 to –0.62), ––– 2020 Assessment Technology Health I2 = 0%, number of trials = 2, n = 66 ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Mindfulness SMD –0.43 (95% CI –0.73 to –0.13), SMD –0.41 (95% CI –0.79 to –0.02), –– I2 = 0%, number of trials = 3, n = 186 I2 = 0%, number of trials = 2, n = 109 Non-trauma-focused CBT SMD –0.05 (95% CI –0.48 to 0.39), ––– I2 = 10%, number of trials = 2, n = 93

Single-component and SMD –1.14 (95% CI –1.54 to –0.74), SMD –0.85 (95% CI –1.42 to –0.29), –– trauma-focused interventions I2 = 86.6%, number of trials = 17, n = 1034 I2 = 62.5%, number of trials = 4, n = 174

Multicomponent and SMD –0.75 (95% CI –1.22 to –0.29), ––– trauma-focused interventions I2 = 58.6%, number of trials = 5, n = 267

Single-component non-trauma- SMD –0.48 (95% CI –0.72 to –0.25), SMD –0.30, (95% CI –0.56 to –0.04), –– focused interventions I2 = 42.0%, number of trials = 10, n = 594 I2 = 0%, number of trials = 5, n = 236 o.2 o 43 No. 24 Vol. Phase-based interventions Effect size –1.03 (95% CI –1.43 to –0.63), ––– I2 = 10.9%, number of trials = 4, n = 133 247 248 PEDX9 APPENDIX IRJunl Library Journals NIHR

Anxiety www.journalslibrary.nihr.ac.uk

TABLE 37 Effectiveness of psychological interventions on anxiety outcomes for all trauma populations

Control Active control

Psychological interventions vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

All SMD –0.81 (95% CI –1.18 to –0.46), ––– I2 = 83.4%, number of trials = 13, n = 1136

Trauma-focused CBT SMD –0.60 (95% CI –1.01 to –0.19), ––– I2 = 85.5%, number of trials = 8, n = 832

EMDR SMD –1.05 (95% CI –1.50 to –0.61), ––– I2 = 9.2%, number of trials = 4, n = 102 IPT ––––

Mindfulness ––––

Non-trauma-focused CBT ––––

Single-component and trauma-focused SMD –0.76 (95% CI –1.15 to –0.37), ––– interventions I2 = 81.5%, number of trials = 10, n = 757

Multicomponent and trauma-focused SMD –0.85 (95% CI –1.60 to –0.10), ––– interventions I2 = 80.4%, number of trials = 3, n = 223

Single-component non-trauma-focused SMD –0.18 (95% CI –0.53 to 0.17), ––– interventions I2 = 26.9%, number of trials = 2, n = 225

Phase-based interventions –––– erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Quality of life

TABLE 38 Effectiveness of psychological interventions on quality-of-life outcomes for all trauma populations

Control Active control

Psychological interventions vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

All SMD 0.28 (95% CI –0.15 to 0.71), ––– I2 = 65.5%, number of trials = 5, n = 307

Trauma-focused CBT SMD 0.23 (95% CI –0.33 to 0.79), ––– I2 = 73.9%, number of trials = 4, n = 260 tal. et EMDR –––– 2020 Assessment Technology Health ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under IPT ––––

Mindfulness ––––

Non-trauma-focused CBT ––––

Single-component and trauma-focused –––– interventions

Multicomponent and trauma-focused –––– interventions

Single-component non-trauma-focused –––– interventions Phase-based interventions –––– o.2 o 43 No. 24 Vol. 249 250 PEDX9 APPENDIX IRJunl Library Journals NIHR www.journalslibrary.nihr.ac.uk Sleep quality

TABLE 39 Effectiveness of psychological interventions on sleep quality outcomes for all trauma populations

Control Active control

Psychological interventions vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

All SMD –1.00 (95% CI –1.49 to –0.51), ––– I2 = 28.8%, number of trials = 3, n = 111

Trauma-focused CBT SMD –1.30 (95% CI –1.87 to –0.73), ––– I2 = 0%, number of trials = 2, n = 59

EMDR ––––

IPT ––––

Mindfulness ––––

Non-trauma-focused CBT ––––

Single-component and trauma-focused interventions ––––

Multicomponent and trauma-focused interventions –––– Single-component non-trauma-focused interventions ––––

Phase-based interventions –––– erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: Effectiveness of psychological interventions by trauma exposure rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Veterans

TABLE 40 Effectiveness of psychological interventions for veteran populations

Control Active control Psychological interventions Follow-up after Outcome vs. control Post treatment Follow-up after < 6 months Post treatment < 6 months

PTSD symptoms All SMD –0.48 (95% CI –0.72 to –0.24), SMD –0.20 (95% CI –0.72 to 0.33), SMD –0.44 (95% CI –0.98 to 0.10), – I2 = 41.7%, number of trials = 14, n = 502 I2 = 63.1%, number of trials = 4, n = 180 I2 = 64%, number of trials = 4, n = 188 Trauma-focused CBT SMD –0.77 (95% CI –1.20 to –0.33), – SMD –0.26 (95% CI –0.88 to 0.35), – I2 = 44.6%, number of trials = 5, n = 199 I2 = 51.1%, number of trials = 2, n = 126

EMDR SMD –0.58 (95% CI –1.00 to –0.16), ––– I2 = 11.1%, number of trials = 4, n = 106 tal. et IPT –––– 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Mindfulness SMD –0.26 (95% CI –0.55 to 0.04), SMD –0.08 (95% CI –0.68 to 0.52), –– I2 = 0%, number of trials = 3, n = 186 I2 = 59%, number of trials = 2, n = 109

Non-trauma-focused –––– CBT

Single-component SMD –0.51 (95% CI –0.79 to –0.23), ––– and trauma-focused I2 = 0%, number of trials = 7, n = 219 interventions

Multicomponent SMD –1.05 (95% CI –1.80 to –0.30), ––– and trauma-focused I2 = 59.4%, number of trials = 3, n = 86 interventions

Single-component SMD –0.16 (95% CI –0.42 to 0.10), SMD 0.01 (95% CI –0.36 to 0.36), –– 2 2

non-trauma-focused I = 0%, number of trials = 4, n = 244 I = 28.1%, number of trials = 3, n = 167 43 No. 24 Vol. interventions

Phase-based –––– interventions continued 251 252 PEDX9 APPENDIX IRJunl Library Journals NIHR

TABLE 40 Effectiveness of psychological interventions for veteran populations (continued) www.journalslibrary.nihr.ac.uk Control Active control Psychological interventions Follow-up after Outcome vs. control Post treatment Follow-up after < 6 months Post treatment < 6 months

Depression All SMD –0.56 (95% CI –0.84 to –0.28), SMD –0.38 (95% CI –0.78 to 0.01), –– symptoms I2 = 46.8%, number of trials = 11, n = 445 I2 = 42.3%, number of trials = 5, n = 201

Trauma-focused SMD –1.02 (95% CI –1.72 to –0.32), ––– CBT I2 = 51%, number of trials = 3, n = 112

EMDR SMD –0.91 (95% CI –2.28 to 0.47), ––– I2 = 77.7%, number of trials = 2, n = 44

IPT ––––

Mindfulness SMD –0.43 (95% CI –0.73 to –0.13), SMD –0.41 (95% CI –0.79 to –0.02), –– I2 = 0%, number of trials = 3, n = 186 I2 = 0%, number of trials = 2, n = 109

Non-trauma-focused –––– CBT Single-component SMD –0.87 (95% CI –1.50 to –0.24), ––– and trauma-focused I2 = 56%, number of trials = 4, n = 133 interventions

Multicomponent SMD –0.86 (95% CI –1.89 to 0.17), ––– and trauma-focused I2 = 61.4%, number of trials = 2, n = 44 interventions

Single-component SMD –0.33 (95% CI –0.61 to –0.05), SMD –0.27 (95% CI –0.56 to 0.02), –– non-trauma-focused I2 = 20.7%, number of trials = 5, n = 268 I2 = 0%, number of trials = 4, n = 188 interventions

Phase-based –––– interventions erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Control Active control Psychological interventions Follow-up after Outcome vs. control Post treatment Follow-up after < 6 months Post treatment < 6 months

Anxiety symptoms All SMD –0.74 (95% CI –1.29 to –0.18), ––– I2 = 54%, number of trials = 5, n = 153 Trauma-focused SMD –0.63 (95% CI –1.83 to 0.57), ––– CBT I2 = 71.3%, number of trials = 2, n = 90 EMDR SMD –0.89 (95% CI –1.45 to –0.33), ––– I2 = 10.6%, number of trials = 3, n = 63

IPT ––––

Mindfulness –––– tal. et elhTcnlg seset2020 Assessment Technology Health Non-trauma-focused –––– ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under CBT

Single-component –––– and trauma-focused interventions

Multicomponent –––– and trauma-focused interventions

Single-component –––– non trauma-focused interventions

Phase-based ––––

interventions 43 No. 24 Vol. 253 254 PEDX9 APPENDIX IRJunl Library Journals NIHR

War-affected populations www.journalslibrary.nihr.ac.uk

TABLE 41 Effectiveness of psychological interventions for war-affected populations

Control Active control Psychological interventions Outcome vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

PTSD symptoms All SMD –0.46 (95% CI –0.68 to –0.25), ––– I2 = 50.4%, number of trials = 8, n = 933 Trauma-focused CBT SMD –0.48 (95% CI –0.82 to –0.15), ––– I2 = 74.8%, number of trials = 6, n = 713 EMDR –––– IPT –––– Mindfulness –––– Non-trauma-focused CBT –––– Single-component and SMD –0.51 (95% CI –0.80 to –0.23), ––– trauma-focused interventions I2 = 55.9%, number of trials = 5, n = 566 Multicomponent and SMD –0.41 (95% CI –0.80 to –0.02), ––– trauma-focused interventions I2 = 48.3%, number of trials = 3, n = 253 Single-component non-trauma- –––– focused interventions Phase-based interventions –––– erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI:

Control Active control rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s Psychological interventions Outcome vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

Depression symptoms All –––– Trauma-focused CBT SMD –0.48 (95% CI –0.82 to –0.15), ––– I2 = 74.8%, number of trials = 6, n = 827 EMDR –––– IPT –––– Mindfulness –––– Non-trauma-focused CBT –––– Single-component and SMD –0.47 (95% CI –0.89 to –0.05), ––– trauma-focused interventions I2 = 79.1%, number of trials = 4, n = 536 Multicomponent and SMD –0.44 (95% CI –1.34 to 0.45), ––– trauma-focused interventions I2 = 79.1%, number of trials = 2, n = 177 Single-component non-trauma- –––– focused interventions tal. et Phase-based interventions –––– 2020 Assessment Technology Health ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Anxiety symptoms All –––– Trauma-focused CBT SMD –0.64 (95% CI –1.18 to –0.10), ––– I2 = 90.4%, number of trials = 5, n = 691 EMDR –––– IPT –––– Mindfulness –––– Non-trauma-focused CBT –––– Single-component and SMD –0.70 (95% CI –1.48 to 0.08), ––– trauma-focused interventions I2 = 94.3%, number of trials = 3, n = 514 Multicomponent and SMD –0.52 (95% CI –1.53 to 0.50), ––– o.2 o 43 No. 24 Vol. trauma-focused interventions I2 = 83.7%, number of trials = 2, n = 177 Single-component non-trauma- –––– focused interventions Phase-based interventions –––– 255 256 PEDX9 APPENDIX IRJunl Library Journals NIHR

Childhood sexual abuse www.journalslibrary.nihr.ac.uk

TABLE 42 Effectiveness of psychological interventions for childhood sexual abuse populations

Control Active control Psychological interventions Outcome vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

PTSD All SMD –0.90 (95% CI –1.43 to –0.37), SMD –0.27 (95% CI –0.71, 0.17), –– symptoms I2 = 89.6%, number of trials = 9, n = 687 I2 = 53.6%, number of trials = 3, n = 323 Trauma-focused CBT SMD –1.22 (95% CI –2.40 to –0.05), ––– I2 = 90.3%, number of trials = 3, n = 153 EMDR –––– IPT –––– Mindfulness –––– Non-trauma-focused CBT SMD 0.01 (95% CI –0.20 to 0.21), ––– I2 = 0%, number of trials = 2, n = 368 Single-component and trauma- SMD –1.19 (95% CI –2.04 to –0.35), ––– focused interventions I2 = 85.5%, number of trials = 4, n = 192 Multicomponent and trauma- –––– focused interventions Single-component non-trauma- SMD –0.54 (95% CI –1.05 to –0.03), SMD –0.08 (95% CI –0.31 to 0.15), –– focused interventions I2 = 83.4%, number of trials = 5, n = 494 I2 = 0%, number of trials = 2, n = 295 Phase-based interventions –––– erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI:

Depression All SMD –0.82 (95% CI –1.10 to –0.55), SMD –0.52 (95% CI –0.99 to –0.04), –– symptoms I2 = 0%, number of trials = 5, n = 234 I2 = 0%, number of trials = 2, n = 76 Trauma-focused CBT SMD –0.50 (95% CI –0.95 to –0.05), ––– I2 = 0%, number of trials = 2, n = 79 EMDR –––– IPT –––– Mindfulness –––– Non-trauma-focused CBT –––– Single-component and trauma- SMD –0.58 (95% CI –0.95 to –0.21), ––– focused interventions I2 = 0%, number of trials = 3, n = 118 Multicomponent and trauma- –––– focused interventions Single-component non-trauma- SMD –0.92 (95% CI –1.36 to –0.48), –––

tal. et 2 focused interventions I = 0%, number of trials = 2, n = 93 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Phase-based interventions –––– Anxiety All –––– symptoms Trauma-focused CBT –––– EMDR –––– IPT –––– Mindfulness –––– Non-trauma-focused CBT –––– Single-component and trauma- SMD –0.87 (95% CI –1.76 to 0.03), ––– focused interventions I2 = 75.2%, number of trials = 2, n = 90 –––– Multicomponent and trauma- 43 No. 24 Vol. focused interventions Single-component non-trauma- –––– focused interventions Phase-based interventions –––– 257 258 PEDX9 APPENDIX IRJunl Library Journals NIHR Refugee populations

TABLE 43 Effectiveness of psychological interventions for refugee populations www.journalslibrary.nihr.ac.uk

Psychological Control Active control interventions Outcome vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

PTSD All SMD –1.84 (95% CI –2.18 to –1.49), SMD –0.66 (95% CI –1.22 to –0.09), –– symptoms I2 = 0%, number of trials = 6, n = 188 I2 = 72.7%, number of trials = 3, n = 235 Trauma-focused SMD –2.12 (95% CI –2.71 to –1.53), SMD –0.40 (95% CI –0.87 to 0.06), –– CBT I2 = 0%, number of trials = 3, n = 71 I2 = 40.1%, number of trials = 2, n = 165 EMDR SMD –1.72 (95% CI –2.19 to –1.26), – SMD –0.15 (95% CI –0.62 to 0.32), SMD –0.15 (95% CI –0.80 to 0.49), I2 = 0%, number of trials = 2, n = 99 I2 = 0%, number of trials = 2, n = 71 I2 = 22.4%, number of trials = 2, n = 71

IPT –– ––

Mindfulness –– ––

Non-trauma-focused –– –– CBT

Single-component SMD –1.87 (95% CI –2.24 to –1.51), SMD –0.67 (95% CI –1.65 to 0.32), –– and trauma-focused I2 = 0%, number of trials = 5, n = 170 I2 = 86.3%, number of trials = 2, n = 133 interventions Multicomponent and –– –– trauma-focused interventions

Single-component –– –– non-trauma-focused interventions

Phase-based –– –– interventions erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Psychological Control Active control interventions Outcome vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months Depression All SMD –1.56 (95% CI –1.93 to –1.16), SMD –0.73 (95% CI –1.57 to 0.10), –– symptoms I2 = 0%, number of trials = 5, n = 148 I2 = 81.3%, number of trials = 2, n = 133 Trauma-focused SMD –2.03 (95% CI –2.92 to –1.13), SMD –0.73 (95% CI –1.57 to 0.10), –– CBT I2 = 0%, number of trials = 2, n = 31 I2 = 81.3%, number of trials = 2, n = 133

EMDR SMD –1.46 (95% CI –1.90 to –1.01), – SMD –0.32 (95% CI –1.23 to 0.59), SMD –0.01 (95% CI –0.47 to 0.45), I2 = 0%, number of trials = 2, n = 99 I2 = 47.8%, number of trials = 2, I2 = 0%, number of trials = 2, n = 73 n = 72

IPT –– –– Mindfulness –– –– tal. et Non-trauma-focused –– –– 2020 Assessment Technology Health CBT ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under Single-component SMD –1.57 (95% CI –1.97 to –1.17), SMD –0.73 (95% CI –1.57 to 0.10), –– and trauma-focused I2 = 0%, number of trials = 4, n = 130 I2 = 81.3%, number of trials = 2, n = 133 interventions Multicomponent and –– –– trauma-focused interventions

Single-component –– –– non-trauma-focused interventions Phase-based –– –– interventions o.2 o 43 No. 24 Vol. continued 259 260 PEDX9 APPENDIX IRJunl Library Journals NIHR www.journalslibrary.nihr.ac.uk TABLE 43 Effectiveness of psychological interventions for refugee populations (continued)

Psychological Control Active control interventions Outcome vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

Anxiety All –– –– symptoms Trauma-focused –– –– CBT

EMDR ––

IPT –– ––

Mindfulness –– ––

Non-trauma-focused –– –– CBT

Single-component –– –– and trauma-focused interventions

Multicomponent and –– –– trauma-focused interventions

Single-component –– –– non-trauma-focused interventions

Phase-based –– –– interventions erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: Domestic violence rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

TABLE 44 Effectiveness of psychological interventions for domestic violence populations

Control Active control Psychological interventions Outcome vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

PTSD symptoms All ––––

Trauma-focused CBT SMD –2.92 (95% CI –3.45 to –2.39), ––– I2 = 0%, number of trials = 2, n = 117

EMDR ––––

IPT ––––

Mindfulness –––– Non-trauma-focused CBT –––– tal. et Single-component and –––– 2020 Assessment Technology Health

ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under trauma-focused interventions

Multicomponent and –––– trauma-focused interventions

Single-component non-trauma- –––– focused interventions

Phase-based interventions ––––

Depression All –––– symptoms Trauma-focused CBT SMD –3.24 (95% CI –4.40 to –2.09), ––– I2 = 66.6%, number of trials = 2, n = 117 EMDR –––– o.2 o 43 No. 24 Vol. IPT ––––

Mindfulness ––––

Non-trauma-focused CBT –––– continued 261 262 PEDX9 APPENDIX IRJunl Library Journals NIHR

TABLE 44 Effectiveness of psychological interventions for domestic violence populations (continued) www.journalslibrary.nihr.ac.uk Control Active control Psychological interventions Outcome vs. control Post treatment Follow-up after < 6 months Post treatment Follow-up after < 6 months

Single-component and trauma- –––– focused interventions

Multicomponent and trauma- –––– focused interventions Single-component non-trauma- –––– focused interventions

Phase-based interventions ––––

Anxiety symptoms All –––– Trauma-focused CBT ––––

EMDR ––––

IPT ––––

Mindfulness ––––

Non-trauma-focused CBT ––––

Single-component and trauma- –––– focused interventions

Multicomponent and trauma- –––– focused interventions

Single-component non-trauma- –––– focused interventions Phase-based interventions –––– DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Pharmacological interventions

All studies included in analyses were conducted in veteran populations.

Post-traumatic stress disorder

TABLE 45 Effectiveness of pharmacological interventions on PTSD outcomes for veteran populations

Pharmacological Placebo interventions vs. placebo Post treatment Follow-up after < 6 months

All ––

Antidepressants SMD –0.50 (95% CI –1.22 to 0.22), I2 = 87%, – number of trials = 6, n = 338

SSRIs SMD –0.61 (95% CI –1.64 to 0.41), I2 = 92.2%, – number of trials = 4, n = 293

Antipsychotics SMD –0.45 (95% CI –0.85 to –0.05), I2 = 51.2%, – number of trials = 5, n = 365

Anticonvulsants SMD –0.16 (95% CI –0.77 to 0.45), I2 = 45.5%, – number of trials = 2, n = 106

Prazosin SMD –0.52 (95% CI –1.03 to –0.02), I2 = 41.4%, – number of trials = 3, n = 110

Depression

TABLE 46 Effectiveness of pharmacological interventions on depression outcomes for veteran populations

Pharmacological Placebo interventions vs. placebo Post treatment Follow-up after < 6 months

All ––

Antidepressants SMD 0.07 (95% CI –0.20 to 0.34), I2 = 0%, – number of trials = 3, n = 220

SSRIs ––

Antipsychotics SMD –0.71 (95% CI –1.44 to 0.03), I2 = 58.3%, – number of trials = 2, n = 266

Anticonvulsants SMD 0.02 (95% CI –0.37 to 0.40), I2 = 0%, – number of trials = 2, n = 106 Prazosin SMD –0.37 (95% CI –1.21 to 0.47), I2 = 68.5%, – number of trials = 2, n = 76

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 263 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 9

Psychosis

TABLE 47 Effectiveness of pharmacological interventions on psychosis outcomes for veteran populations

Pharmacological Placebo interventions vs. Outcome placebo Post treatment Follow-up after < 6 months

PANSS-positive All ––

Antidepressants ––

SSRIs ––

Antipsychoticsa Mean difference –1.75 (95% CI –4.04 to 0.54), – I2 = 76.9%, number of trials = 3, n = 329

Anticonvulsants ––

Prazosin ––

PANSS-negative All –– Antidepressants ––

SSRIs ––

Antipsychoticsa Mean difference 0.54 (95% CI –0.14 to 1.22), – I2 = 0%, number of trials = 2, n = 284 Anticonvulsants ––

Prazosin ––

PANSS: total All ––

Antidepressants ––

SSRIs ––

Antipsychoticsa Mean difference 0.04 (95% CI –2.08 to 2.16), – I2 = 0%, number of trials = 2, n = 284

Anticonvulsants ––

Prazosin ––

PANSS: general All –– psychopathology Antidepressants –– SSRIs ––

Antipsychoticsa Mean difference –0.18 (95% CI –1.39 to 1.03), – I2 = 0%, number of trials = 2, n = 284 Anticonvulsants ––

Prazosin –– a All antipsychotics were risperidone.

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Sleep quality

TABLE 48 Effectiveness of pharmacological interventions on sleep quality outcomes for veteran populations

Pharmacological Placebo interventions vs. placebo Post treatment Follow-up after < 6 months

All ––

Antidepressants ––

SSRIs ––

Antipsychotics –– Anticonvulsants ––

Prazosin SMD –0.73 (95% CI –1.12 to –0.34), I2 = 0%, – number of trials = 3, n = 109

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 265 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 10 Forest plots of results of effectiveness meta-analyses

Psychological interventions versus control in all trauma populations

Post-traumatic stress disorder symptoms

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Krupnick (2008)98 32 16 – 1.37 (– 2.03 to – 0.71) 72.19

Meffert (2014)108 10 8 – 1.51 (– 2.58 to – 0.44) 27.81

Overall (I2 = 0.0%; p = 0.826) – 1.41 (– 1.97 to – 0.85) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 27 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all IPT interventions with control.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 267 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Adenauer (2011)55 11 8 –1.88 (–2.99 to –0.77) 3.78 Bolton (2014)62 101 66 –0.43 (–0.74 to –0.11) 5.86 Chard (2005)66 36 37 –2.33 (–2.93 to –1.73) 5.20 Franklin (2017)81 6 7 –1.05 (–2.22 to 0.13) 3.61 Hermenau (2013)86 15 15 –0.41 (–1.13 to 0.31) 4.85 Hinton (2005)89 20 20 –2.17 (–2.96 to –1.38) 4.67 Hinton (2004)90 6 6 –2.40 (–3.94 to –0.85) 2.77 Jung (2013)92 14 14 –0.83 (–1.61 to –0.06) 4.71 Keane (1989)94 11 31 –0.24 (–0.93 to 0.45) 4.95 Knaevelsrud (2015)96 79 80 –0.92 (–1.25 to –0.59) 5.83 Kubany (2003)100 18 14 –2.99 (–4.02 to –1.96) 3.99 Kubany (2004)101 45 40 –2.89 (–3.51 to –2.28) 5.16 Margolies (2011)105 15 12 –1.12 (–1.94 to –0.30) 4.58 McDonagh (2005)106 29 23 –0.50 (–1.06 to 0.06) 5.31 McLay (2011)107 10 9 –0.68 (–1.61 to 0.25) 4.27 Miyahira (2012)109 10 12 –0.50 (–1.35 to 0.35) 4.48 Reger (2016)126 30 47 –0.40 (–0.86 to 0.07) 5.54 Ulmer (2011)140 12 9 –1.81 (–2.85 to –0.77) 3.97 Wang (2016)143 13 15 0.01 (–0.74 to 0.75) 4.80 Weiss (2015) trial 1: CETA144 99 50 –0.70 (–1.05 to –0.35) 5.79 Weiss (2015) trial 2: CPT144 124 64 –0.26 (–0.56 to 0.05) 5.87

Overall (I2 = 86.0%; p = 0.000) –1.09 (–1.44 to –0.75) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 012 3 Favours intervention Favours control

FIGURE 28 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all trauma-focused CBT interventions with control. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

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First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.70 (–2.56 to –0.84) 13.41

Acarturk (2016)54 37 33 –2.17 (–2.77 to –1.58) 15.91

Carlson (1997)64 10 10 –0.94 (–1.85 to –0.04) 12.94

Devilly (1998)74 12 10 –0.03 (–0.87 to 0.81) 13.58

Edmond (1999)76 20 19 –1.09 (–1.77 to –0.42) 15.15

Himmerich (2016)88 21 17 –0.47 (–1.12 to 0.18) 15.40

Jensen (1994)91 13 12 –1.00 (–1.84 to –0.17) 13.61

Overall (I2 = 75.4%; p = 0.000) –1.07 (–1.65 to –0.50) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 29 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all EMDR interventions with control.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Kearney (2013)95 25 22 –0.50 (–1.08 to 0.08) 26.26

Possemato (2016)121 36 26 –0.05 (–0.55 to 0.45) 34.96

Wahbeh (2016)142 52 25 –0.27 (–0.75 to 0.20) 38.78

Overall (I2 = 0.0%; p = 0.517) –0.26 (–0.55 to 0.04) 100.00

NOTE: weights are from random-effects analysis

– 2 – 1 012 Favours intervention Favours control

FIGURE 30 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all mindfulness interventions with control.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 269 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Bolton (2014)62 114 66 –0.25 (–0.64 to 0.14) 19.49

Engel (2015)78 29 29 0.13 (–0.38 to 0.65) 11.08

Sikkema (2007)131 73 48 0.09 (–0.27 to 0.45) 22.15

Sikkema (2013)132 124 123 –0.03 (–0.28 to 0.22) 47.28

Overall (I2 = 0.0%; p = 0.566) –0.03 (–0.20 to 0.14) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 31 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all non-trauma-focused CBT interventions with control.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.20 (–2.00 to –0.41) 5.82 Acarturk (2016)54 37 33 –1.74 (–2.29 to –1.18) 6.61 Adenauer (2011)55 11 8 –2.05 (–3.19 to –0.91) 4.67 Bolton (2014)62 101 66 –0.38 (–0.69 to –0.06) 7.24 Carlson (1998)64 10 11 –1.64 (–2.64 to –0.64) 5.12 Devilly (1998)74 13 10 –0.23 (–1.06 to 0.59) 5.71 Edmond (1999)76 20 19 –0.74 (–1.39 to –0.09) 6.31 Franklin (2017)81 6 7 –1.60 (–2.88 to –0.32) 4.25 Hinton (2004)89 6 6 –1.99 (–3.42 to –0.56) 3.83 Jung (2013)92 14 14 –0.49 (–1.25 to 0.26) 5.96 Knaevelsrud (2015)96 79 80 –1.03 (–1.36 to –0.70) 7.20 Kubany (2003)100 18 14 –3.97 (–5.19 to –2.75) 4.42 Kubany (2004)101 45 40 –2.77 (–3.37 to –2.17) 6.47 McDonagh (2005)106 29 22 –0.51 (–1.07 to 0.05) 6.58 Miyahira (2012)109 10 12 0.09 (–0.75 to 0.93) 5.67 Reger (2016)126 30 46 –0.56 (–1.03 to –0.09) 6.86 Weiss (2015) trial 2: CPT144 124 64 –0.28 (–0.59 to 0.02) 7.26

Overall (I2 = 86.6%; p = 0.000) –1.14 (–1.54 to –0.74) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 012 3 Favours intervention Favours control

FIGURE 32 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all single-component trauma-focused interventions with control. CPT, cognitive processing therapy.

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First author (year) Intervention Control ES (95% CI) Weight (%) (n) (n)

Chard (2005)66 36 37 –2.33 (–2.93 to –1.73) 13.02

Cloitre (2002)69 22 24 –1.30 (–1.93 to –0.66) 12.71

Himmerich (2016)88 21 17 –0.47 (–1.12 to 0.18) 12.64

Margolies (2011)105 15 12 –1.12 (–1.94 to –0.30) 11.32

Ulmer (2011)140 12 9 –1.81 (–2.85 to –0.77) 9.69

Wang (2016)143 13 15 0.01 (–0.74 to 0.75) 11.92

Weiss (2015) trial 1 CETA144 99 50 –0.70 (–1.05 to –0.35) 14.66

Yeomans (2010)145 38 38 –0.28 (–0.73 to 0.17) 14.04

Overall (I2 = 83.5%; p = 0.000) –0.97 (–1.49 to –0.45) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 33 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all multicomponent trauma-focused interventions with control. CETA, common elements treatment approach.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Bolton (2014)62 114 66 –0.25 (–0.64 to 0.14) 11.03

Engel (2015)78 29 29 0.13 (–0.38 to 0.65) 9.40

Kearney (2013)95 25 22 –0.50 (–1.08 to 0.08) 8.59

Krupnick (2008)98 32 16 –1.37 (–2.03 to –0.71) 7.69

McDonagh (2005)106 22 23 –0.89 (–1.50 to –0.28) 8.22

Meffert (2014)108 10 8 –1.51 (–2.58 to –0.44) 4.43

Possemato (2016)121 36 26 –0.05 (–0.55 to 0.45) 9.54

Sikkema (2007)131 73 48 0.09 (–0.27 to 0.45) 11.34

Sikkema (2013)132 124 123 –0.03 (–0.28 to 0.22) 12.74

Wahbeh (2016)142 52 25 –0.27 (–0.75 to 0.20) 9.86

Zlotnick (1997)146 16 17 –0.85 (–1.57 to –0.14) 7.15

Overall (I2 = 69.6%; p = 0.000) –0.39 (–0.66 to –0.12) 100.00

NOTE: weights are from random-effects analysis

–1.0 –0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 34 Meta-analysis of post-treatment effect size (ES) for PTSD total symptoms, comparing all single-component non-trauma-focused interventions with control.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 271 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

Complex post-traumatic stress disorder symptoms

First author (year) Intervention Control SMD (95% CI) Weight (%) (n) (n)

Feske (2008)79 9 12 –1.02 (–1.95 to –0.10) 26.51

Hermenau (2013)86 15 15 0.11 (–0.61 to 0.83) 33.46

McDonagh (2005)106 29 23 0.17 (–0.38 to 0.72) 40.03

Overall (I2 = 60.6%; p = 0.079) –0.17 (–0.82 to 0.49) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 35 Meta-analysis of post-treatment SMD for emotional dysregulation, comparing trauma-focused CBT interventions with control.

First author (year) Intervention Control SMD (95% CI) Weight (%) (n) (n)

Krupnick (2008)98 32 16 0.09 (–0.51 to 0.69) 27.52

McDonagh (2005)106 22 23 0.08 (–0.51 to 0.66) 28.61

Meffert (2014)108 10 8 –0.97 (–1.96 to 0.02) 12.19

Wahbeh (2016)142 27 25 0.09 (–0.46 to 0.63) 31.67

Overall (I2 = 23.9%; p = 0.268) –0.04 (–0.41 to 0.33) 100.00

NOTE: weights are from random-effects analysis

– 2 – 1 021 Favours intervention Favours control

FIGURE 36 Meta-analysis of post-treatment SMD for emotional dysregulation, comparing single-component and non-trauma-focused interventions with control.

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First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Jung (2013)92 14 14 0.76 (–0.01 to 1.53) 33.75

Kubany (2003)100 18 14 3.07 (2.03 to 4.12) 31.31

Kubany (2004)101 45 40 2.88 (2.27 to 3.49) 34.94

Overall (I2 = 90.4%; p = 0.000) 2.22 (0.75 to 3.70) 100.00

NOTE: weights are from random-effects analysis

– 3 – 2 – 1 012 3 Favours control Favours intervention

FIGURE 37 Meta-analysis of post-treatment SMD for negative self-concept, comparing all trauma-focused CBT interventions with control (positive SMD equals improvement in symptoms).

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Kubany (2003)100 18 14 3.07 (2.03 to 4.12) 25.46

Kubany (2004)101 45 40 2.88 (2.27 to 3.49) 74.54

Overall (I2 = 0.0%; p = 0.753) 2.93 (2.40 to 3.45) 100.00

NOTE: weights are from random-effects analysis

– 3 – 2 – 10 1 23 Favours control Favours intervention

FIGURE 38 Meta-analysis of post-treatment SMD for negative self-concept, comparing all multicomponent and trauma-focused interventions with control (positive SMD equals improvement in symptoms).

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Reed (2006)125 10 10 1.81 (0.75 to 2.87) 42.46

Wahbeh (2016)142 25 25 0.64 (0.07 to 1.21) 57.54

Overall (I2 = 72.6%; p = 0.056) 1.14 (0.00 to 2.27) 100.00

NOTE: weights are from random-effects analysis

– 3 – 2 – 10 1 23 Favours control Favours intervention

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 273 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Cloitre (2002)69 22 24 –0.94 (–1.55 to –0.33) 49.72

Krupnick (2008)98 32 16 –0.23 (–0.84 to 0.37) 50.28

Overall (I2 = 61.9%; p = 0.105) –0.59 (–1.28 to 0.11) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 40 Meta-analysis of post-treatment SMD for interpersonal problems, comparing all psychological interventions with control.

Depression symptoms

First author (year) Intervention Control ES (95% CI) Weight (%) (n) (n)

Bolton (2014)62 101 66 –0.38 (–0.69 to –0.06) 7.87 Chard (2005)66 36 37 –2.00 (–2.57 to –1.44) 7.12 Franklin (2017)81 6 7 –1.60 (–2.88 to –0.32) 4.54 Jung (2013)92 14 14 –0.49 (–1.25 to 0.26) 6.43 Knaevelsrud (2015)96 79 80 –1.03 (–1.36 to –0.70) 7.82 Kubany (2003)100 18 14 –3.97 (–5.19 to –2.75) 4.72 Kubany (2004)101 45 40 –2.77 (–3.37 to –2.17) 7.00 Margolies (2011)105 14 9 –1.40 (–2.33 to –0.46) 5.73 McDonagh (2005)106 29 22 –0.51 (–1.07 to 0.05) 7.12 Miyahira (2012)109 10 12 0.09 (–0.75 to 0.93) 6.10 Reger (2016)126 30 46 –0.56 (–1.03 to –0.09) 7.43 Ulmer (2011)140 12 9 –0.34 (–1.22 to 0.53) 5.98 Wang (2016)143 13 15 0.08 (–0.67 to 0.82) 6.47 Weiss (2015) trial 1: CETA144 99 50 –0.84 (–1.20 to –0.49) 7.77 Weiss (2015) trial 2: CPT144 124 64 –0.28 (–0.59 to 0.02) 7.89

Overall (I2 = 88.5%; p = 0.000) –0.99 (–1.40 to –0.59) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 012 3 Favours intervention Favours control

FIGURE 41 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all trauma-focused CBT interventions with control. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

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First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.20 (–2.00 to –0.41) 19.29

Acarturk (2016)54 37 33 –1.74 (–2.29 to –1.18) 24.11

Carlson (1997)64 10 11 –1.64 (–2.64 to –0.64) 15.74

Devilly (1998)74 13 10 –0.23 (–1.06 to –0.59) 18.71

Edmond (1999)76 20 19 –0.74 (–1.39 to –0.09) 22.14

Overall (I2 = 65.2%; p = 0.022) –1.12 (–1.68 to –0.55) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 42 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all EMDR interventions with control.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Krupnick (2008)98 32 16 –1.06 (–1.70 to –0.42) 73.36

Meffert (2014)108 10 8 –1.46 (–2.52 to –0.40) 26.64

Overall (I2 = 0.0%; p = 0.524) –1.17 (–1.71 to –0.62) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 43 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all IPT interventions with control.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 275 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Kearney (2013)95 25 22 –0.62 (–1.21 to –0.03) 26.14

Possemato (2016)121 36 26 –0.28 (–0.78 to 0.23) 35.08

Wahbeh (2016)142 52 25 –0.43 (–0.92 to 0.05) 38.78

Overall (I2 = 0.0%; p = 0.685) –0.43 (–0.73 to –0.13) 100.00

NOTE: weights are from random-effects analysis

– 2 – 1 012 Favours intervention Favours control

FIGURE 44 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all mindfulness interventions with control.

First author (year) Intervention Control ES (95% CI) Weight (n) (n) (%)

Engel (2015)78 29 29 0.13 (–0.39 to 0.64) 61.39

Teng (2008)137 18 17 –0.33 (–0.99 to 0.34) 38.61

Overall (I2 = 10.0%; p = 0.292) –0.05 (–0.48 to 0.39) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 45 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all non-trauma-focused CBT interventions with control.

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First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.20 (–2.00 to –0.41) 5.82 Acarturk (2016)54 37 33 –1.74 (–2.29 to –1.18) 6.61 Adenauer (2011)55 11 8 –2.05 (–3.19 to –0.91) 4.67 Bolton (2014)62 101 66 –0.38 (–0.69 to –0.06) 7.24 Carlson (1997)64 10 11 –1.64 (–2.64 to –0.64) 5.12 Devilly (1998)74 13 10 –0.23 (–1.06 to 0.59) 5.71 Edmond (1999)76 20 19 –0.74 (–1.39 to –0.09) 6.31 Franklin (2017)81 6 7 –1.60 (–2.88 to –0.32) 4.25 Hinton (2004)89 6 6 –1.99 (–3.42 to –0.56) 3.83 Jung (2013)92 14 14 –0.49 (–1.25 to 0.26) 5.96 Knaevelsrud (2015)96 79 80 –1.03 (–1.36 to –0.70) 7.20 Kubany (2003)100 18 14 –3.97 (–5.19 to –2.75) 4.42 Kubany (2004)101 45 40 –2.77 (–3.37 to –2.17) 6.47 McDonagh (2005)106 29 22 –0.51 (–1.07 to 0.05) 6.58 Miyahira (2012)109 10 12 0.09 (–0.75 to 0.93) 5.67 Reger (2016)126 30 46 –0.56 (–1.03 to –0.09) 6.86 Weiss (2015) trial 2: CPT144 124 64 –0.28 (–0.59 to 0.02) 7.26

Overall (I2 = 86.6%; p = 0.000) –1.14 (–1.54 to –0.74) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 012 3 Favours intervention Favours control

FIGURE 46 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all single-component and trauma-focused CBT interventions with control. CPT, cognitive processing therapy.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Chard (2005)66 36 37 –2.00 (–2.57 to –1.44) 18.09

Cloitre (2002)69 22 24 –1.22 (–1.85 to –0.59) 17.31

Margolies (2011)105 14 9 –1.40 (–2.33 to –0.46) 13.78

Ulmer (2011)140 12 9 –0.34 (–1.22 to 0.53) 14.52

Wang (2016)143 13 15 0.08 (–0.67 to 0.82) 16.01

Weiss (2015) trial 1: CETA144 99 50 –0.84 (–1.20 to –0.49) 20.59

Overall (I2 = 79.4%; p = 0.000) –0.98 (–1.54 to –0.41) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 47 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all multicomponent and trauma-focused interventions with control. CETA, common elements treatment approach.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 277 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Bolton (2014)62 114 66 –0.28 (–0.58 to 0.03) 17.83

Engel (2015)78 29 29 0.13 (–0.39 to 0.64) 11.46

Kearney (2013)95 25 22 –0.62 (–1.21 to –0.03) 9.84

Krupnick (2008)98 32 16 –1.06 (–1.70 to –0.42) 8.86

McDonagh (2005)106 22 23 –0.78 (–1.39 to –0.18) 9.43

Meffert (2014)108 10 8 –1.46 (–2.52 to –0.40) 4.13

Moradi (2014)111 12 12 –0.72 (–1.55 to 0.11) 6.13

Possemato (2016)121 36 26 –0.28 (–0.78 to 0.23) 11.66

Teng (2008)137 18 17 –0.33 (–0.99 to 0.34) 8.35

Wahbeh (2016)142 52 25 –0.43 (–0.92 to 0.05) 12.30

Overall (I2 = 42.0%; p = 0.078) –0.48 (–0.72 to –0.25) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 48 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing all single-component and non-trauma-focused interventions with control.

Anxiety symptoms

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Carlson (1997)64 10 11 –1.39 (–2.36 to –0.43) 19.71

Devilly (1998)74 13 10 –0.43 (–1.27 to 0.40) 25.66

Edmond (1999)76 20 19 –1.35 (–2.05 to –0.65) 35.13

Jensen (1994)91 11 8 –0.99 (–1.96 to –0.02) 19.50

Overall (I2 = 9.2%; p = 0.347) –1.05 (–1.50 to –0.61) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 00.5 1.0 Favours intervention Favours control

FIGURE 49 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing EMDR interventions with control.

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First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Bolton (2014)62 101 66 –0.25 (–0.56 to 0.06) 12.81

Carlson (1997)64 10 11 –1.39 (–2.36 to –0.43) 7.58

Devilly (1998)74 13 10 –0.43 (–1.27 to 0.40) 8.56

Edmond (1999)76 20 19 –1.35 (–2.05 to –0.65) 9.67

Franklin (2017)81 6 7 –1.39 (–2.63 to –0.16) 5.87

Jensen (1994)91 11 8 –0.99 (–1.96 to –0.02) 7.55

Knaevelsrud (2015)96 79 80 –1.55 (–1.90 to –1.19) 12.51

McDonagh (2005)106 29 22 –0.43 (–0.99 to 0.13) 10.86

Reger (2016)126 30 47 –0.14 (–0.59 to 0.32) 11.72

Weiss (2015) trial 2: CPT144 124 64 –0.33 (–0.63 to –0.03) 12.87

Overall (I2 = 81.5%; p = 0.000) –0.76 (–1.15 to –0.37) 100.00

NOTE: weights are from random-effects analysis

–3 –2 –1 0 123 Favours intervention Favours control

FIGURE 50 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing single-component and trauma-focused interventions with control. CPT, cognitive processing therapy.

First author (year) Intervention Control ES (95% CI) Weight (n) (n) (%)

Cloitre (2002)69 22 24 –1.54 (–2.21 to –0.88) 31.74

Wang (2016)143 13 15 0.06 (–0.68 to 0.80) 29.85

Weiss (2015) trial 1: CETA144 99 50 –0.98 (–1.34 to –0.62) 38.41

Overall (I2 = 80.4%; p = 0.006) –0.85 (–1.60 to –0.10) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 51 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing multicomponent and trauma-focused interventions with control. CETA, common elements treatment approach.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 279 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Bolton (2014)62 114 66 –0.07 (–0.37 to 0.24) 71.39

McDonagh (2005)106 22 23 –0.46 (–1.06 to 0.13) 28.61

Overall (I2 = 26.9%; p = 0.242) –0.18 (–0.53 to 0.17) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 52 Meta-analysis of post-treatment effect size (ES) for anxiety symptoms, comparing single-component and non-trauma-focused interventions with control.

Quality of life

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Knaevelsrud (2015)96 79 80 0.84 (0.51 to 1.16) 31.60

McDonagh (2005)106 29 23 0.14 (–0.40 to 0.69) 26.42

Miyahira (2012)109 10 12 –0.23 (–1.08 to 0.61) 19.66

Wang (2016)143 12 15 –0.12 (–0.84 to 0.60) 22.32

Overall (I2 = 73.9%; p = 0.009) 0.23 (–0.33 to 0.79) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours control Favours intervention

FIGURE 53 Meta-analysis of post-treatment effect size (ES) for quality of life, comparing trauma-focused CBT interventions with control (positive ES favours intervention).

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Sleep quality

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Margolies (2011)105 20 17 –1.23 (–1.94 to –0.52) 33.39

Ulmer (2011)140 13 9 –1.43 (–2.39 to –0.47) 21.07

Wahbeh (2016)142 27 25 –0.63 (–1.19 to –0.07) 45.54

Overall (I2 = 28.8%; p = 0.245) –1.00 (–1.49 to –0.51) 100.00

NOTE: weights are from random-effects analysis

– 3 – 2 – 1 021 3 Favours intervention Favours control

FIGURE 54 Meta-analysis of post-treatment effect size (ES) for sleep quality, comparing all psychological interventions with control.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Margolies (2011)105 20 17 –1.23 (–1.94 to –0.52) 64.68

Ulmer (2011)140 13 9 –1.43 (–2.39 to –0.47) 35.32

Overall (I2 = 0.0%; p = 0.747) –1.30 (–1.87 to –0.73) 100.00

NOTE: weights are from random-effects analysis

– 3 – 2 – 10 1 2 3 Favours intervention Favours control

FIGURE 55 Meta-analysis of post-treatment effect size (ES) for sleep quality, comparing trauma-focused CBT interventions with control.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 281 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

Psychological interventions versus control in trauma subgroups

Veterans

Post-traumatic stress disorder symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Franklin (2017)81 6 7 –1.05 (–2.22 to 0.13) 10.21

Keane (1989)94 11 31 –0.24 (–0.93 to 0.45) 19.81

Margolies (2011)105 15 12 –1.12 (–1.94 to –0.30) 16.44

McLay (2011)107 10 9 –0.68 (–1.61 to 0.25) 14.13

Reger (2016)126 30 47 –0.40 (–0.86 to 0.07) 27.22

Ulmer (2011)140 12 9 –1.81 (–2.85 to –0.77) 12.19

Overall (I2 = 44.6%; p = 0.108) –0.77 (–1.20 to –0.33) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 56 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing trauma-focused CBT interventions with control in veteran populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Carlson (1997)64 10 11 –0.94 (–1.85 to –0.04) 19.54

Devilly (1998)74 12 10 –0.03 (–0.87 to 0.81) 22.52

Himmerich (2016)88 21 17 –0.47 (–1.12 to 0.18) 35.29

Jensen (1994)91 13 12 –1.00 (–1.84 to –0.17) 22.65

Overall (I2 = 11.1%; p = 0.337) –0.58 (–1.00 to –0.16) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 57 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing EMDR interventions with control in veteran populations.

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First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Kearney (2013)95 25 22 –0.50 (–1.08 to 0.08) 26.26

Possemato (2016)121 36 26 –0.05 (–0.55 to 0.45) 34.96

Wahbeh (2016)142 52 25 –0.27 (–0.75 to 0.20) 38.78

Overall (I2 = 0.0%; p = 0.517) –0.26 (–0.55 to 0.04) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 58 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing mindfulness interventions with control in veteran populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Carlson (1997)64 10 11 –0.94 (–1.85 to –0.04) 9.54

Devilly (1998)74 12 10 –0.03 (–0.87 to 0.81) 11.16

Franklin (2017)81 6 7 –1.05 (–2.22 to 0.13) 5.69

Jensen (1994)91 13 12 –1.00 (–1.84 to –0.17) 11.23

Keane (1989)94 11 31 –0.24 (–0.93 to 0.45) 16.51

McLay (2011)107 10 9 –0.68 (–1.61 to 0.25) 9.10

Reger (2016)126 30 47 –0.40 (–0.86 to 0.07) 36.76

Overall (I2 = 0.0%; p = 0.515) –0.51 (–0.79 to –0.23) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 59 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and trauma- focused interventions with control in veteran populations.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 283 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention Control SMD (95% CI) Weight (n) (n) (%)

Himmerich (2016)88 21 17 –0.47 (–1.12 to 0.18) 39.54

Margolies (2011)105 15 12 –1.12 (–1.94 to –0.30) 33.52

Ulmer (2011)140 12 9 –1.81 (–2.85 to –0.77) 26.94

Overall (I2 = 59.4%; p = 0.085) –1.05 (–1.80 to –0.30) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 60 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing multicomponent and trauma-focused interventions with control in veteran populations.

First author (year) Intervention Control SMD (95% CI) Weight (n) (n) (%)

Engel (2015)78 29 29 0.13 (–0.38 to 0.65) 25.10

Kearney (2013)95 25 22 –0.50 (–1.08 to 0.08) 19.67

Possemato (2016)121 36 26 –0.05 (–0.55 to 0.45) 26.19

Wahbeh (2016)142 52 25 –0.27 (–0.75 to 0.20) 29.05

Overall (I2 = 0.0%; p = 0.399) –0.16 (–0.42 to 0.10) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 61 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and non-trauma-focused interventions with control in veteran populations.

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Depression symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Franklin (2017)81 6 7 –1.60 (–2.88 to –0.32) 13.47

Margolies (2011)105 14 9 –1.40 (–2.33 to –0.46) 21.15

Reger (2016)126 30 46 –0.56 (–1.03 to –0.09) 42.12

Ulmer (2011)140 12 9 –0.34 (–1.22 to –0.53) 23.26

Overall (I2 = 39.8%; p = 0.173) –0.83 (–1.35 to –0.30) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 00.5 1.0 Favours intervention Favours control

FIGURE 62 Meta-analysis of post-treatment SMD for total depression symptoms, comparing trauma-focused CBT interventions with control in veteran populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Carlson (1997)64 10 11 –1.64 (–2.64 to –0.64) 47.89

Devilly (1998)74 13 10 –0.23 (–1.06 to 0.59) 52.11

Overall (I2 = 77.7%; p = 0.034) –0.91 (–2.28 to 0.47) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.50 0.5 1.0 Favours intervention Favours control

FIGURE 63 Meta-analysis of post-treatment SMD for total depression symptoms, comparing EMDR interventions with control in veteran populations.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 285 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Kearney (2013)95 25 22 –0.62 (–1.21 to –0.03) 26.14

Possemato (2016)121 36 26 –0.28 (–0.78 to 0.23) 35.08

Wahbeh (2016)142 52 25 –0.43 (–0.92 to 0.05) 38.78

Overall (I2 = 0.0%; p = 0.685) –0.43 (–0.73 to –0.13) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 64 Meta-analysis of post-treatment SMD for total depression symptoms, comparing mindfulness interventions with control in veteran populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Carlson (1997)64 10 11 –1.64 (–2.64 to –0.64) 21.36

Devilly (1998)74 13 10 –0.23 (–1.06 to 0.59) 25.79

Franklin (2017)81 6 7 –1.60 (–2.88 to –0.32) 15.97

Reger (2016)126 30 46 –0.56 (–1.03 to –0.09) 36.88

Overall (I2 = 56.0%; p = 0.078) –0.87 (–1.50 to –0.24) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 00.5 1.0 Favours intervention Favours control

FIGURE 65 Meta-analysis of post-treatment SMD for total depression symptoms, comparing single-component and trauma-focused interventions with control in veteran populations.

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First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Margolies (2011)105 14 9 –1.40 (–2.33 to –0.46) 48.58

Ulmer (2011)140 12 9 –0.34 (–1.22 to 0.53) 51.42

Overall (I2 = 61.4%; p = 0.107) –0.86 (–1.89 to 0.17) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.50 0.5 1.0 Favours intervention Favours control

FIGURE 66 Meta-analysis of post-treatment SMD for total depression symptoms, comparing multicomponent and trauma-focused interventions with control in veteran populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Engel (2015)78 29 29 0.13 (–0.39 to 0.64) 22.74

Kearney (2013)95 25 22 –0.62 (–1.21 to –0.03) 18.52

Moradi (2014)111 12 12 –0.72 (–1.55 to 0.11) 10.30

Possemato (2016)121 36 26 –0.28 (–0.78 to 0.23) 23.31

Wahbeh (2016)142 52 25 –0.43 (–0.92 to 0.05) 25.13

Overall (I2 = 20.7%; p = 0.283) –0.33 (–0.61 to –0.05) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 67 Meta-analysis of post-treatment SMD for total depression symptoms, comparing single-component and non-trauma-focused interventions with control in veteran populations.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 287 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

Anxiety symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Franklin (2017)81 6 7 –1.39 (–2.63 to –0.16) 39.13

Reger (2016)126 30 47 –0.14 (–0.59 to 0.32) 60.87

Overall (I2 = 71.3%; p = 0.062) –0.63 (–1.83 to 0.57) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.50 0.5 1.0 Favours intervention Favours control

FIGURE 68 Meta-analysis of post-treatment SMD for total anxiety symptoms, comparing trauma-focused CBT interventions with control in veteran populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Carlson (1997)64 10 11 –1.39 (–2.36 to –0.43) 30.47

Devilly (1998)74 13 10 –0.43 (–1.27 to 0.40) 39.37

Jensen (1994)91 11 8 –0.99 (–1.96 to –0.02) 30.16

Overall (I2 = 10.6%; p = 0.327) –0.89 (–1.45 to –0.33) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 69 Meta-analysis of post-treatment SMD for total anxiety symptoms, comparing EMDR interventions with control in veteran populations.

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War-affected populations

Post-traumatic stress disorder symptoms

First author (year) Intervention Control ES (95% CI) Weight (%) (n) (n)

Bolton (2014)62 101 66 –0.43 (–0.74 to –0.11) 20.10

Hermenau (2013)86 15 15 –0.41 (–1.13 to 0.31) 7.81

Knaevelsrud (2015)96 79 80 –0.92 (–1.25 to –0.59) 19.47

Miyahira (2012)109 10 12 –0.50 (–1.35 to 0.35) 6.03

Wang (2016)143 13 15 0.01 (–0.74 to 0.75) 7.51

Weiss (2015) trial 1: 99 50 –0.70 (–1.05 to –0.35) 18.48 CETA144 Weiss (2015) trial 2: 124 64 –0.26 (–0.56 to 0.05) 20.61 CPT144

Overall (I2 = 50.0%; p = 0.062) –0.51 (–0.74 to –0.28) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 70 Meta-analysis of post-treatment effect size (ES) for total PTSD symptoms, comparing trauma-focused CBT interventions with control in war-affected populations. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Wang (2016)143 13 15 0.01 (–0.74 to 0.75) 19.66

Weiss (2015) trial 1: 99 50 –0.70 (–1.05 to –0.35) 44.51 CETA144 Yeomans (2010)145 38 38 –0.28 (–0.73 to 0.17) 35.83

Overall (I2 = 48.3%; p = 0.145) –0.41 (–0.80 to –0.02) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 71 Meta-analysis of post-treatment effect size (ES) for total PTSD symptoms, comparing multicomponent trauma-focused interventions with control in war-affected populations. CETA, common elements treatment approach.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 289 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

Depression symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Bolton (2014)62 101 66 –0.38 (–0.69 to –0.06) 28.61

Knaevelsrud (2015)96 79 80 –1.03 (–1.36 to –0.70) 28.08

Miyahira (2012)109 10 12 –0.09 (–0.75 to 0.93) 14.41

Weiss (2015) trial 2: 124 64 –0.28 (–0.59 to 0.02) 28.90 CPT144

Overall (I2 = 79.1%; p = 0.002) –0.47 (–0.89 to –0.05) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 72 Meta-analysis of post-treatment SMD for depression symptoms, comparing single-component and trauma- focused interventions with control in war-affected populations. CPT, cognitive processing therapy.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Wang (2016)143 13 15 0.08 (–0.67 to 0.82) 43.40

Weiss (2015) trial 1: 99 50 –0.84 (–1.20 to –0.49) 56.60 CETA144

Overall (I2 = 79.1%; p = 0.029) –0.44 (–1.34 to 0.45) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 73 Meta-analysis of post-treatment effect size (ES) for depression symptoms, comparing multicomponent and trauma-focused interventions with control in war-affected populations. CETA, common elements treatment approach.

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Anxiety symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Bolton (2014)62 101 66 –0.25 (–0.56 to 0.06) 33.48

Knaevelsrud (2015)96 79 80 –1.55 (–1.90 to –1.19) 32.95

Weiss (2015) trial 2: CPT144 124 64 –0.33 (–0.63 to –0.03) 33.57

2 Overall (I = 94.3%; p = 0.000) –0.70 (–1.48 to 0.08) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 74 Meta-analysis of post-treatment SMD for total anxiety symptoms, comparing single-component and trauma-focused interventions with control in war-affected populations. CPT, cognitive processing therapy.

First author (year) Intervention (n) Control (n) ES (95% CI) Weight (%)

Wang (2016)143 13 15 0.06 (–0.68 to 0.80) 44.92

Weiss (2015) trial 1: 99 50 –0.98 (–1.34 to –0.62) 55.08 CETA144

Overall (I2 = 83.7%; p = 0.013) –0.52 (–1.53 to 0.50) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 75 Meta-analysis of post-treatment effect size (ES) for total anxiety symptoms, comparing multicomponent and trauma-focused interventions with control in war-affected populations. CETA, common elements treatment approach.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 291 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

Childhood sexual abuse populations

Post-traumatic stress disorder symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Chard (2005)66 36 37 –2.33 (–2.93 to –1.73) 33.83

Jung (2013)92 14 14 –0.83 (–1.61 to –0.06) 31.94

McDonagh (2005)106 29 23 –0.50 (–1.06 to –0.06) 34.23

Overall (I2 = 90.3%; p = 0.000) –1.22 (–2.40 to –0.05) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 76 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing trauma-focused CBT interventions with control in childhood sexual abuse populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Sikkema (2007)131 73 48 0.09 (–0.27 to 0.45) 31.91

Sikkema (2013)132 124 123 –0.03 (–0.28 to 0.22) 68.09

Overall (I2 = 0.0%; p = 0.587) 0.01 (–0.20 to 0.21) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 77 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing non-trauma-focused CBT interventions with control in childhood sexual abuse populations.

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First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Edmond (1999)76 20 19 –1.09 (–1.77 to –0.42) 30.88

Jung (2013)92 14 14 –0.83 (–1.61 to –0.06) 23.50

McDonagh (2005)106 29 23 –0.50 (–1.06 to –0.06) 45.61

Overall (I2 = 0.0%; p = 0.403) –0.76 (–1.14 to –0.39) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 78 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and trauma-focused interventions with control in childhood sexual abuse populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Krupnick (2008)98 32 16 –1.37 (–2.03 to –0.71) 17.83

McDonagh (2005)106 22 23 –0.89 (–1.50 to –0.28) 18.62

Sikkema (2007)131 73 48 0.09 (–0.27 to 0.45) 22.55

Sikkema (2013)132 124 123 –0.03 (–0.28 to 0.22) 24.01

Zlotnick (1997)146 16 17 –0.85 (–1.57 to –0.14) 16.99

Overall (I2 = 83.4%; p = 0.000) –0.54 (–1.05 to –0.03) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 79 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and non-trauma-focused interventions with control in childhood sexual abuse populations.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 293 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

Depression symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Chard (2005)66 36 37 –2.00 (–2.57 to –1.44) 34.16

Jung (2013)92 14 14 –0.49 (–1.25 to 0.26) 31.65

McDonagh (2005)106 29 22 –0.51 (–1.07 to 0.05) 34.19

Overall (I2 = 87.9%; p = 0.000) –1.01 (–2.05 to 0.02) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 80 Meta-analysis of post-treatment SMD for depression symptoms, comparing trauma-focused CBT interventions with control in childhood sexual abuse populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Edmond (1999)76 20 19 –0.74 (–1.39 to –0.09) 32.49

Jung (2013)92 14 14 –0.49 (–1.25 to 0.26) 24.22

McDonagh (2005)106 29 22 –0.51 (–1.07 to 0.05) 43.28

Overall (I2 = 0.0%; p = 0.844) –0.58 (–0.95 to –0.21) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 81 Meta-analysis of post-treatment SMD for depression symptoms, comparing single-component and trauma-focused interventions with control in childhood sexual abuse populations.

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First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Krupnick (2008)98 32 16 –1.06 (–1.70 to –0.42) 47.55

McDonagh (2005)106 22 23 –0.78 (–1.39 to –0.18) 52.45

Overall (I2 = 0.0%; p = 0.538) –0.92 (–1.36 to –0.48) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 82 Meta-analysis of post-treatment SMD for depression symptoms, comparing single-component and non-trauma-focused interventions with control in childhood sexual abuse populations.

Anxiety symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

McDonagh (2005)106 29 22 –0.43 (–0.99 to 0.13) 52.69

Edmond (1999)76 20 19 –1.35 (–2.05 to –0.65) 47.31

Overall (I2 = 75.2%; p = 0.045) –0.87 (–1.76 to 0.03) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 83 Meta-analysis of post-treatment SMD for anxiety symptoms, comparing single-component and trauma-focused interventions with control in childhood sexual abuse populations.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 295 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

Refugee populations

Post-traumatic stress disorder symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Adenauer (2011)55 11 8 –1.88 (–2.99 to –0.77) 28.65

Hinton (2005)89 20 20 –2.17 (–2.96 to –1.38) 56.59

Hinton (2004)90 6 6 –2.40 (–3.94 to –0.85) 14.75

Overall (I2 = 0.0%; p = 0.852) –2.12 (–2.71 to –1.53) 100.00

NOTE: weights are from random-effects analysis

– 1.0– 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 84 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing trauma-focused CBT interventions with control in refugee populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.70 (–2.56 to –0.84) 29.32

Acarturk (2016)54 37 33 –1.74 (–2.29 to –1.18) 70.68

Overall (I2 = 0.0%; p = 0.944) –1.72 (–2.19 to –1.26) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.50 0.5 1.0 Favours intervention Favours control

FIGURE 85 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing EMDR interventions with control in refugee populations.

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First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.70 (–2.56 to –0.84) 18.18

Acarturk (2016)54 37 33 –1.74 (–2.29 to –1.18) 43.82

Adenauer (2011)55 11 8 –1.88 (–2.99 to –0.77) 10.89

Hinton (2005)89 20 20 –2.17 (–2.96 to –1.38) 21.51

Hinton (2004)90 6 6 –2.40 (–3.94 to –0.85) 5.61

Overall (I2 = 0.0%; p = 0.847) –1.87 (–2.24 to –1.51) 100.00

NOTE: weights are from random-effects analysis

– 1.0– 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 86 Meta-analysis of post-treatment SMD for total PTSD symptoms, comparing single-component and trauma-focused interventions with control in refugee populations.

Depression symptoms

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Adenauer (2011)55 11 8 –2.05 (–3.19 to –0.91) 61.06

Hinton (2004)90 6 6 –1.99 (–3.42 to –0.56) 38.94

Overall (I2 = 0.0%; p = 0.953) –2.03 (–2.92 to –1.13) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.50 0.5 1.0 Favours intervention Favours control

FIGURE 87 Meta-analysis of post-treatment SMD for depression symptoms, comparing trauma-focused CBT interventions with control in refugee populations.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 297 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.20 (–2.00 to –0.41) 31.39

Acarturk (2016)54 37 33 –1.57 (–2.11 to –1.03) 68.61

Overall (I2 = 0.0%; p = 0.455) –1.46 (–1.90 to –1.01) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.50 0.5 1.0 Favours intervention Favours control

FIGURE 88 Meta-analysis of post-treatment SMD for depression symptoms, comparing EMDR interventions with control in refugee populations.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Acarturk (2015)53 15 14 –1.20 (–2.00 to –0.41) 25.11

Acarturk (2016)54 37 33 –1.57 (–2.11 to –1.03) 54.89

Adenauer (2011)55 11 8 –2.05 (–3.19 to –0.91) 12.22

Hinton (2004)90 6 6 –1.99 (–3.42 to –0.56) 7.79

Overall (I2 = 0.0%; p = 0.612) –1.57 (–1.97 to –1.17) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 00.5 1.0 Favours intervention Favours control

FIGURE 89 Meta-analysis of post-treatment SMD for depression symptoms, comparing single-component and trauma-focused interventions with control in refugee populations.

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Pharmacological interventions versus placebo

Post-traumatic stress disorder symptoms

First author (year) Intervention Control SMD (95% CI) Weight (n) (n) (%)

Becker (2007)59 15 7 –0.22 (–1.12 to 0.68) 15.44

Davis (2004)73 14 9 –0.23 (–1.07 to 0.61) 15.93

Friedman (2007)82 86 83 0.08 (–0.22 to 0.38) 19.61

Naylor (2013)112 5 7 0.23 (–0.92 to 1.38) 13.39

Panahi (2011)118 35 35 –1.86 (–2.43 to –1.30) 18.07

Zohar (2002)147 23 19 –0.78 (–1.41 to –0.15) 17.58

Overall (I2 = 87.0%; p = 0.000) –0.50 (–1.22 to 0.22) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 90 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing antidepressants with placebo.

First author (year) Intervention Control SMD (95% CI) Weight (n) (n) (%)

Friedman (2007)82 86 83 0.08 (–0.22 to 0.38) 27.60

Naylor (2013)112 5 7 0.23 (–0.92 to 1.38) 20.82

Panahi (2011)118 35 35 –1.86 (–2.43 to –1.30) 26.05

Zohar (2002)147 23 19 –0.78 (–1.41 to –0.15) 25.53

Overall (I2 = 92.2%; p = 0.000) –0.61 (–1.64 to 0.41) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 00.5 1.0 Favours intervention Favours control

FIGURE 91 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing SSRIs with placebo.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 299 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Bartzokis (2005)58 22 25 –0.65 (–1.24 to –0.06) 21.95

Hamner (2003)85 19 18 0.07 (–0.58 to 0.71) 20.00

Krystal (2011)99 123 124 –0.21 (–0.46 to 0.04) 36.44

Monnelly (2003)110 7 8 –1.35 (–2.49 to –0.21) 9.40

Stein (2002)135 10 9 –0.96 (–1.92 to –0.01) 12.21

Overall (I2 = 51.2%; p = 0.085) –0.45 (–0.85 to –0.05) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 92 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing antipsychotics with placebo.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Davis (2008)72 41 41 0.07 (–0.36 to 0.50) 65.90

Lindley (2007)104 9 15 –0.59 (–1.43 to 0.26) 34.10

Overall (I2 = 45.5%; p = 0.176) –0.16 (–0.77 to 0.45) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 93 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing anticonvulsants with placebo.

First author (year) Intervention (n) Control (n) SMD (95% CI) Weight (%)

Germain (2012)84 15 13 –0.12 (–0.86 to 0.63) 29.39

Raskind (2007)122 17 17 –0.38 (–1.06 to 0.30) 32.86

Raskind (2013)123 23 25 –0.97 (–1.57 to –0.37) 37.75

Overall (I2 = 41.4%; p = 0.182) –0.52 (–1.03 to –0.02) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 94 Meta-analysis of post-treatment SMD for PTSD symptoms, comparing prazosin with placebo.

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Depression symptoms

First author (year) Intervention Control SMD (95% CI) Weight (n) (n) (%)

Becker (2007)59 18 10 –0.05 (–0.83 to 0.72) 11.90

Davis (2004)73 14 9 –0.27 (–1.12 to 0.57) 10.05

Friedman (2007)82 86 83 0.14 (–0.17 to 0.44) 78.05

Overall (I2 = 0.0%; p = 0.632) 0.07 (–0.20 to 0.34) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 95 Meta-analysis of post-treatment SMD for depression symptoms, comparing antidepressants with placebo.

First author (year) Intervention Control SMD (95% CI) Weight (n) (n) (%)

Krystal (2011)99 123 124 –0.45 (–0.70 to –0.20) 68.34

Stein (2002)135 10 9 –1.26 (–2.25 to –0.26) 31.66

Overall (I2 = 58.3%; p = 0.122) –0.71 (–1.44 to 0.03) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.50 0.5 1.0 Favours intervention Favours control

FIGURE 96 Meta-analysis of post-treatment SMD for depression symptoms, comparing antipsychotics with placebo.

First author (year) Intervention Control SMD (95% CI) Weight (n) (n) (%)

Davis (2008)72 41 41 –0.07 (–0.50 to 0.36) 78.70

Lindley (2007)104 9 15 0.33 (–0.50 to 1.17) 21.30

Overall (I2 = 0.0%; p = 0.397) 0.02 (–0.37 to 0.40) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.5 0 0.5 1.0 Favours intervention Favours control

FIGURE 97 Meta-analysis of post-treatment SMD for depression symptoms, comparing anticonvulsants with placebo.

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Psychosis symptoms

First author (year) Intervention (n) Control (n) WMD (95% CI) Weight (%)

Bartzokis (2005)58 22 23 –3.63 (–6.12 to –1.14) 29.12

Hamner (2003)85 19 18 –2.20 (–4.88 to 0.48) 27.65

Krystal (2011)99 123 124 –0.20 (–0.76 to 0.36) 43.23

Overall (I2 = 76.9%; p = 0.013) –1.75 (–4.04 to 0.54) 100.00

NOTE: weights are from random-effects analysis

– 4 – 2 024 Favours intervention Favours control

FIGURE 98 Meta-analysis of post-treatment weighted mean difference (WMD) for positive psychotic symptoms, comparing risperidone with placebo.

First author (year) Intervention (n) Control (n) WMD (95% CI) Weight (%)

Hamner (2003)85 19 18 –0.20 (–3.52 to 3.12) 4.16

Krystal (2011)99 123 124 0.57 (–0.12 to 1.26) 95.84

Overall (I2 = 0.0%; p = 0.657) 0.54 (–0.14 to 1.22) 100.00

NOTE: weights are from random-effects analysis

– 1.0 – 0.50 0.5 1.0 Favours intervention Favours control

FIGURE 99 Meta-analysis of post-treatment weighted mean difference (WMD) for negative psychotic symptoms, comparing risperidone with placebo.

First author (year) Intervention (n) Control (n) WMD (95% CI) Weight (%)

Hamner (2003)85 19 18 –4.20 (–15.03 to 6.63) 3.84

Krystal (2011)99 123 124 0.21 (–1.95 to 2.37) 96.16

Overall (I2 = 0.0%; p = 0.434) 0.04 (–2.08 to 2.16) 100.00

NOTE: weights are from random-effects analysis

– 10 – 55010 Favours intervention Favours control

FIGURE 100 Meta-analysis of post-treatment weighted mean difference (WMD) for total psychotic symptoms, comparing risperidone with placebo.

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First author (year) Intervention (n) Control (n) WMD (95% CI) Weight (%)

Hamner (2003)85 19 18 –1.80 (–7.80 to 4.20) 4.08

Krystal (2011)99 123 124 –0.11 (–1.35 to 1.13) 95.92

Overall (I2 = 0.0%; p = 0.589) –0.18 (–1.39 to 1.03) 100.00

NOTE: weights are from random-effects analysis

– 10 – 55010 Favours intervention Favours control

FIGURE 101 Meta-analysis of post-treatment weighted mean difference (WMD) for general psychopathology symptoms, comparing risperidone with placebo.

Attrition meta-analyses

Veterans

First author (year) Intervention (n) Control (n) OR (95% CI) Weight (%)

Carlson (1998)64 23 12 6.13 (0.23 to 162.50) 3.27

Chard (2005)66 36 35 1.04 (0.34 to 3.16) 13.34

Engel (2015)78 43 37 0.59 (0.18 to 1.95) 12.57

Franklin (2017)81 19 8 0.04 (0.00 to 0.70) 3.81

Gamito (2010)83 73 0.62 (0.02 to 19.58) 2.98

Kearney (2013)95 25 22 0.55 (0.05 to 6.49) 5.17

Margolies (2013)105 20 20 1.71 (0.40 to 7.34) 10.39

McDonagh (2005)106 51 23 0.40 (0.10 to 1.55) 11.13

McLay (2011)107 10 10 3.32 (0.12 to 91.60) 3.20

Miyahira (2012)109 29 13 0.21 (0.05 to 0.94) 10.14

Possemato (2016)121 36 26 0.07 (0.01 to 0.33) 9.44

Resick (2015)128 56 52 0.43 (0.16 to 1.15) 14.55

Overall (I2 = 41.8%; p = 0.063) 0.49 (0.26 to 0.92) 100.00

NOTE: weights are from random-effects analysis

0.1 0.2 0.3 0.5 1.0 2.0 3.0 5.0 10.0 Favours intervention Favours control

FIGURE 102 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a veteran population.

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 303 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 10

First author (year) Intervention Control OR (95% CI) Weight (n) (n) (%)

Cook (2010)71 61 63 0.23 (0.09 to 0.63) 49.21

Germain (2012)84 17 16 0.80 (0.17 to 3.73) 20.80

Niles (2012)115 17 16 0.46 (0.07 to 2.98) 14.28

Teng (2008)137 18 17 0.27 (0.05 to 1.57) 15.71

Overall (I2 = 0.0%; p = 0.589) 0.34 (0.17 to 0.68) 100.00

NOTE: weights are from random-effects analysis

0.1 0.2 0.3 0.5 1.0 2.0 3.0 5.0 10.0 Favours intervention Favours control

FIGURE 103 Meta-analysis of OR of attrition from all psychological interventions compared with active controls, among a veteran population.

Pharmacological interventions

First author (year) Intervention Control OR (95% CI) Weight (n) (n) (%)

Davis (2004)73 27 15 0.72 (0.20 to 2.58) 20.44

Friedman (2007)82 86 83 0.47 (0.22 to 0.98) 43.29

Panahi (2011)118 35 35 1.78 (0.39 to 8.09) 15.51

van der Kolk (1994)141 33 31 0.26 (0.07 to 0.92) 20.76

Overall (I2 = 24.9%; p = 0.262) 0.56 (0.29 to 1.07) 100.00

NOTE: weights are from random-effects analysis

0.073 1 13.700 Favours intervention Favours control

FIGURE 104 Meta-analysis of OR of attrition from antidepressants compared with placebo, among a veteran population.

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First author (year) Intervention (n) Control (n) OR (95% CI) Weight (%)

Bartzokis (2005)58 33 32 0.03 (0.00 to 0.54) 9.04

Hamner (2003)85 19 18 0.56 (0.15 to 2.10) 25.82

Krystal (2011)99 147 149 1.03 (0.56 to 1.91) 42.78

Monnelly (2003)110 8 8 0.29 (0.01 to 8.37) 7.02

Reich (2004)127 12 9 0.86 (0.11 to 6.62) 15.34

Stein (2002)135 10 9 (Excluded) 0.00

Overall (I2 = 41.8%; p = 0.143) 0.57 (0.22 to 1.48) 100.00

NOTE: weights are from random-effects analysis

0.00169 1 593.00 Favours intervention Favours control

FIGURE 105 Meta-analysis of OR of attrition from antidepsychotics compared with placebo, among a veteran population.

First author (year) Intervention (n) Control (n) OR (95% CI) Weight (%)

Davis (2008)72 44 41 0.70 (0.24 to 2.05) 59.40

Lindley (2007)104 20 20 0.27 (0.07 to 1.04) 40.60

Overall (I2 = 13.3%; p = 0.283) 0.48 (0.19 to 1.18) 100.00

NOTE: weights are from random-effects analysis

0.1 0.2 0.3 0.5 1.0 2.0 3.0 5.0 10.0 Favours intervention Favours control

FIGURE 106 Meta-analysis of OR of attrition from anticonvulsants compared with placebo, among a veteran population.

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Childhood sexual abuse populations

First author (year) Intervention Control OR (95% CI) Weight (n) (n) (%)

Cloitre (2002)69 31 27 0.31 (0.07 to 1.28) 34.73

Jung (2013)92 17 17 1.00 (0.17 to 5.83) 27.07

Krupnick (2008)98 32 16 0.03 (0.00 to 0.62) 12.96

Sikkema (2007)131 197 56 0.10 (0.01 to 1.65) 13.46

Ulmer (2011)140 12 9 0.10 (0.00 to 2.13) 11.78

Overall (I2 = 26.5%; p = 0.245) 0.24 (0.08 to 0.75) 100.00

NOTE: weights are from random-effects analysis

0.1 0.2 0.3 0.5 1.0 2.0 3.0 5.0 10.0 Favours intervention Favours control

FIGURE 107 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a childhood sexual abuse population.

Refugee populations

First author (year) Intervention Control OR (95% CI) Weight (n) (n) (%)

Acarturk (2015)53 49 49 1.49 (0.62 to 3.62) 40.26

Adenauer (2011)55 16 18 2.75 (0.67 to 11.24) 15.85

Hijazi (2014)87 41 22 0.93 (0.08 to 10.85) 5.20

Meffert (2014)108 13 9 0.42 (0.04 to 4.81) 5.25

Stenmark (2013)136 51 30 0.79 (0.30 to 2.07) 33.44

Overall (I2 = 0.0%; p = 0.547) 1.21 (0.69 to 2.12) 100.00

NOTE: weights are from random-effects analysis

0.1 0.2 0.3 0.5 1.0 2.0 3.0 5.0 10.0 Favours intervention Favours control

FIGURE 108 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a refugee population.

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Domestic violence populations

First author (year) Intervention (n) Control (n) OR (95% CI) Weight (%)

Bolton (2014)62 215 66 0.40 (0.19 to 0.84) 59.50

Kubany (2003)100 19 18 5.14 (0.52 to 51.29) 40.50

Overall (I2 = 76.7%; p = 0.038) 1.13 (0.10 to 13.17) 100.00

NOTE: weights are from random-effects analysis

0.1 0.2 0.3 0.5 1.0 2.0 3.0 5.0 10.0 Favours intervention Favours control

FIGURE 109 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a domestic violence population.

War-affected populations

First author (year) Intervention (n) Control (n) OR (95% CI) Weight (%)

Azad Marzabadi (2014)57 16 16 1.00 (0.12 to 8.13) 13.21

Hermenau (2013)86 19 19 0.18 (0.01 to 4.00) 7.03

Knaevelsrud (2015)96 79 80 1.03 (0.55 to 1.94) 39.90

Weiss (2015) trial 1: CETA144 99 50 0.39 (0.02 to 8.20) 7.23

Weiss (2015) trial 2: CPT144 129 64 0.04 (0.00 to 0.62) 8.28

Yeomans (2010)145 82 42 1.13 (0.31 to 4.09) 24.35

Overall (I2 = 36.7%; p = 0.162) 0.66 (0.27 to 1.60) 100.00

NOTE: weights are from random-effects analysis

0.1 0.2 0.3 0.5 1.0 2.0 3.0 4.0 10.0 Favours intervention Favours control

FIGURE 110 Meta-analysis of OR of attrition from all psychological interventions compared with control, among a war-affected population. CETA, common elements treatment approach; CPT, cognitive treatment therapy.

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DOI: 10.3310/hta24430 Health Technology Assessment 2020 Vol. 24 No. 43

Appendix 11 Characteristics of qualitative studies included

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Melton et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in 309 professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. 310 PEDX11 APPENDIX IRJunl Library Journals NIHR

TABLE 49 Characteristics of the qualitative studies included

Authors (year), Population Intervention(s) and Qualitative approach country Aim (sample size) delivery Outcomes and data collection CERQual outcome www.journalslibrary.nihr.ac.uk Bermudez et al. An analysis of the Low-income minority Group MBSR Struggle to practise Semistructured Minimal concerns (2013),163 USA perspectives of women women with a PTSD meditation, vision of interviews/focus group with trauma exposure history exposed to growing and helping, Contributes to existing participating intimate partner violence personal and Thematic analysis knowledge, identifies in mindfulness-based (n = 10) interpersonal (interpretive areas of value to women interventions over time improvement phenomenological experiencing intimate analysis) partner violence

Dutton et al. The use of MBSR as Low-income minority Group MBSR Feasibility, initial interest Follow-up interviews Minimal concerns (2013),164 USA a community-based women with a PTSD to participate intervention to history exposed to Thematic findings Description of method reduce health disparities intimate partner violence Acceptability, congruent lacking for low-income, (n = 53) and relevant to predominantly African participant needs Pilot study to inform American, women with future research. Offers a history of intimate Positive benefits included insight into dropout rates partner violence and increased awareness; and reasons for attrition, PTSD self-acceptance; self- as well as effects of empowerment, non- conflict within the groups reactivity and self-care; decreased distress; increased sense of belonging and compassion

Hughes and Study to examine the Women in domestic Motivational Self-perception, beliefs of Interviews/grounded Minimal concerns Rasmussen use of motivational shelters who have been interviewing vs. abuse causation, beliefs theory (2010),162 USA interviewing with women exposed to domestic treatment as usual of shelter efficacy, Some qualitative receiving services at a violence. Experimental emotions towards abuser, Part of mixed-methods methods reported; domestic violence shelter group (n = 10) and specific statements, study results not thematic control group (n = 10) beliefs of personal (more difficult to were included in the strength pick out) mixed-methods study but not all were included in Pilot study. Valuable to the qualitative review inform future design of (n = 6) full study erdcinsol eadesdt:NH orasLbay ainlIsiuefrHat eerh vlain rasadSuisCodntn ete lh House, Alpha Centre, Coordinating commercial in Studies included for and be Applications may Trials advertising. report) Evaluation, of full Research, form the Health indeed, any (or with for extracts associated Institute and not study National UK. and is 7NS, Library, research SO16 reproduction Journals private Southampton the Park, of NIHR and Science purposes to: Southampton made the of addressed for is University reproduced be acknowledgement freely suitable should be that reproduction may provided issue This journals Care. professional Social and Health for Queen © 10.3310/hta24430 DOI: rne n otolro MO22.Ti okwspoue yMelton by produced was work This 2020. HMSO of Controller and Printer ’s

Authors (year), Population Intervention(s) and Qualitative approach country Aim (sample size) delivery Outcomes and data collection CERQual outcome

Hundt et al. Qualitative interviews to Male and female Prolonged exposure, Patient experience of Qualitative interviews Minimal concerns (2017),166 USA elicit first-hand accounts veterans (n = 23) cognitive processing intervention, perceptions of veterans’ experiences therapy or both of treatment mechanisms Thematic analysis Contributes to body of in these evidence-based (grounded theory). Focus evidence for patient’s psychotherapies is qualitative satisfaction with prolonged exposure treatment and cognitive processing therapy

Martinez et al. Study to better Male and female MBSR vs. no control Barriers to enrolment Semistructured Minimal concerns (2015),165 USA understand the unique veterans (n = 48) and participation interviews/content challenges that may keep analysis Provides insight into veterans referred to barriers to enrolment MBSR from enrolling Some qualitative and participation by and completing the methods reported and veterans in MBSR programme thematic findings. Focus is qualitative tal. et elhTcnlg seset2020 Assessment Technology Health Naved et al. Evaluation of an initiative Women in rural Paramedic-conducted Includes patient In-depth interviews/ Significant concerns ne h em facmisoigcnrc sudb h ertr fState of Secretary the by issued contract commissioning a of terms the under (2009),161 to use paramedics as Bangladesh exposed to mental health counselling experience of the thematic/content analysis regarding recruitment Bangladesh first-level mental health lifetime physical and intervention and data analysis counsellors of abused sexual abuse (n = 30) Part of mixed-methods women in rural design (survey and Mixed-methods design. Bangladesh (2003–2004) interviews) Value in identifying from the perspective of barriers to participation the abused women in low-income rural areas Palmer et al. Inpatient programme for Males and females Group 6-week Includes patient Semistructured Minimal concerns (2007),167 traumatic stress recovery exposed to childhood inpatient programme experience of interviews Canada in which patients were sexual abuse (n = 30) for traumatic stress intervention Useful to inform interviewed after recovery. Community Thematic/constant participant screening discharge about their milieu (group healing), comparison/ethnography. and selection when experiences during safety (supportive Part of a larger designing group-based

treatment environment), addressing quantitative study interventions 43 No. 24 Vol. problematic behaviours, traumatic re-enactment continued 311 312 PEDX11 APPENDIX IRJunl Library Journals NIHR www.journalslibrary.nihr.ac.uk

TABLE 49 Characteristics of the qualitative studies included (continued)

Authors (year), Population Intervention(s) and Qualitative approach country Aim (sample size) delivery Outcomes and data collection CERQual outcome

Parker et al. Qualitative study to Women exposed to Group treatment Includes patient Semistructured No concerns (2007),168 understand how women childhood sexual abuse experience of interviews Canada with a history of child (n = 7) intervention Useful to examine the maltreatment Thematic/ phenomenological experienced the ‘Women phenomenological approach to investigate Recovering from Abuse approach. Focus is the patients’ perspective Program’ (WRAP), an qualitative. Some of the intervention existing intensive group qualitative methods in relation to their treatment programme reported. Thematic own personal lived findings experiences

Vincent et al. This study considers Asylum seekers exposed Trauma-focused CBT for Includes patient Semistructured Minimal concerns (2013),169 UK the acceptability of to trauma (n = 7) PTSD experience of the interviews trauma-focused CBT intervention – Useful insight into for asylum seekers with acceptability Interpretive the challenges of PTSD by exploring their phenomenological examining the value of experiences of treatment analysis interventions on asylum seekers with PTSD

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